Polymerization process with catalyst reactivation

ABSTRACT

Polymerization processes of the present invention comprise low catalyst concentration. Embodiments include a polymerization process comprising polymerizing free radically (co)polymerizable monomers in a polymerization medium comprising one or more radically (co)polymerizable monomers, a transition metal catalyst complex capable of participating in a one electron redox reaction with an ATRP initiator; a free radical initiator; and an ATRP initiator; (wherein the concentration of transition metal catalyst complex in the polymerization medium is less than 100 ppm). Further embodiments include a polymerization process, comprising polymerizing one or more radically (co)polymerizable monomers in the presence of at least one transition metal catalyst complex; an ATRP initiator; and a reducing agent; wherein the transition metal catalyst complex is present at less than 10 −3  mole compared to the moles of radically transferable atoms or groups present on the ATRP initiator.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Divisional application under 35 U.S.C. §121claiming priority to U.S. application Ser. No. 11/990,841, filed Jan.16, 2009, which was a U.S. national stage filing under 35 U.S.C. §371 ofInternational Application No. PCT/US2006/033792, filed Aug. 28, 2006 andclaims benefit of and priority to U.S. Provisional Ser. No. 60/711,722,filed Aug. 26, 2005, U.S. Provisional Ser. No. 60/814,816, filed Jun.19, 2006, and U.S. Provisional Ser. No. 60/814,846, filed Jun. 19, 2006.

TECHNICAL FIELD OF THE INVENTION

The present invention is directed to an atom transfer radicalpolymerization process where the catalyst in the activator state, orcatalytic transfer agent, is continuously regenerated.

BACKGROUND OF THE INVENTION

Since their discovery controlled radical polymerization (“CRP”)processes have gained increasing research and industrial attention. CRPprocesses couple the capability of conventional free radicalpolymerization (“RP”) to (co)polymerize a wide range of monomers withthe ability to synthesize polymeric materials with predeterminedmolecular weight (“MW”), low polydispersity (“PDI”), controlledcomposition, site specific functionality, selected chain topology, andincorporation of biological or inorganic species into the final product.

The three most studied methods of CRP processes are nitroxide mediatedpolymerization (“NMP”), atom transfer radical polymerization (“ATRP”),and degenerative transfer with dithioesters via reversibleaddition-fragmentation chain transfer polymerization (“RAFT”). CRPprocesses typically, but not necessarily, comprise a relatively lowstationary concentration of propagating chain ends in relation todormant chain ends. A dormant chain end comprises a transferable atom orgroup. The dormant chain end may be converted to a propagating chain endby loss of the transferable atom or group to the transition metalcomplex in the lower oxidation state. The low concentration ofpropagating chain ends present during the polymerization process reducesthe probability of bimolecular termination reactions, leading to radicalpolymerization processes that behave as a “living” polymerizationprocess.

The ATRP equilibrium (characterized by K_(ATRP)) most frequentlyinvolves homolytic cleavage of an alkyl (pseudo)halide bond R—X by atransition metal complex activator Mt^(n)/L which (reversibly) generatesan active propagating alkyl radical R^(•) and the corresponding higheroxidation state metal halide deactivator Me^(n+1)X/L in a redox reactionScheme 1.

The active R^(•) may then propagate with a vinyl monomer (M), bedeactivated in this equilibrium reaction by Mt^(n+1)X/L, or terminate byeither coupling or disproportionation with another R^(•). Suchtermination results in an increase in the amount of deactivator,Mt^(n+1)X/L, by two equivalents resulting in an increase inconcentration of dormant species as a result of the persistent radicaleffect. [Fischer, H. Chem. Rev. 2001, 101, 3581-3610.]

In some embodiments of CRP processes, a fast rate of initiation(“R_(i)”), relative to the rate of propagation (“R_(p)”), (For example,where from a process where R_(i)<<R_(p) to a process where R_(i)˜R_(p))contributes to control of the molecular weight, degree of polymerization(“DP_(n)”) and molecular weight distribution. As used herein,DP_(n)˜[M]/[I]₀, where [M] is the moles of monomer polymerized and [I]₀is the initial concentration of the added initiator. Terminationreactions will tend to reduce the control over such properties and sinceCRP processes are radical based polymerization processes, sometermination reactions during a CRP process are unavoidable.

In all radical polymerizations, biradical termination occurs with a rateof termination (“k_(t)”) which is dependent on the concentration ofradicals (“[P*]”) to the power two (R_(t)=k_(t)[P*]²). Therefore, it maybe assumed that at the same rate of propagation (the same concentrationof radicals), generally the same number of chains would terminate,regardless whether the polymerization process is a RP or a CRP. However,this assumption ignores the diffusion effect of the macromoleculeradicals in a CRP. In a RP most chains are terminated by the reaction ofa small radical with a growing polymer radical. In the case of SFRP, orATRP, these initial termination reactions result in an increase in theconcentration of dormant species as a result of the persistent radicaleffect, [Fischer, H. Chem. Rev. 2001, 101, 3581-3610.]

In an RP, all polymer chains are eventually terminated, whereas in CRPthe terminated chains constitute only small fraction of all chains (˜1to 10%) while most polymer chains are in the dormant state. The majorityof polymer chains in a CRP in the dormant state are capable ofreactivation which allows continuation of the polymerization,functionalization, chain extension to form block copolymers, etc. Thus,a CRP behaves as a “living” polymerization process. [Greszta, D. et. al.Macromolecules 1994, 27, 638.] As used herein, “polymer” refers to amacromolecule formed by the chemical union of monomers, typically fiveor more monomers. The term polymer includes homopolymers and copolymersincluding random copolymers, statistical copolymers, alternatingcopolymers, gradient copolymers, periodic copolymers, telechelicpolymers and polymers of any topology or architecture including blockcopolymers, graft polymers, star polymers, bottle-brush polymers, combpolymers, branched or hyperbranched polymers, and such polymers tetheredto particle surfaces or flat surfaces as well as other polymerstructures.

ATRP is the most frequently used CRP technique with a significantcommercial potential for many specialty materials including coatings,sealants, adhesives, dispersants but also materials for health andbeauty products, electronics and biomedical applications. The mostfrequently used ATRP process comprises a reversible halogen atomtransfer catalyzed by redox active transition metal compounds, mostfrequently copper based. ATRP transition metal catalysts typicallycomprise a transition metal complexed with a ligand. In ATRP, radicallypolymerizable monomers are polymerized in the presence of a transitionmetal catalyst. For a list of radically polymerizable monomers, see U.S.Pat. No. 5,763,548, hereby incorporated by reference. It is believedthat the transition metal catalyst participates in a redox reaction withat least one of an ATRP initiator and a dormant polymer chain, seeScheme 1. Suitable transition metal catalysts comprise a transitionmetal and a ligand coordinated to the transition metal. The transitionmetal catalyst participates in a reversible redox reaction with at leastone of an ATRP initiator and a dormant polymer chain. Suitabletransition metal catalysts comprise a transition metal and, optionally,at least one ligand coordinated to the transition metal. The activity ofthe transition metal catalyst depends on the composition of thetransition metal and the ligand.

To function as an ATRP transition metal catalyst, the transition metalmust have at least two readily accessible oxidation states separated byone electron, a higher oxidation state and a lower oxidation state. Thereversible redox reaction results in the transition metal catalystcycling between the higher oxidation state (the “deactivator state”) anda lower oxidation state (the “activator state”) while the polymer chainscycle between having propagating chain ends and dormant chain ends.Typically, the transition metal is one of copper, iron, rhodium, nickel,cobalt, palladium, molybdenum, manganese, rhenium, or ruthenium. In someembodiments, the transition metal catalyst comprises a copper halide,and preferably the copper halide is one of Cu(I) Br or Cu(I)Cl.Living/controlled polymerizations typically, but not necessarily,comprise a relatively low stationary concentration of polymerscomprising propagating chain ends in relation to polymers having dormantchain ends. When the polymer has a dormant chain end, the chain endcomprises the transferable atom or group. The dormant chain end may beconverted to a propagating chain end by transfer of the transferableatom or group to the transition metal catalyst. The description of themechanism of an ATRP is provided for explanation and is not intended tolimit the invention. The disclosed mechanism is generally accepted, butdifferent transition metal catalyst may result in different mechanisms.The ligand affects the structure of the catalyst, the solubilizingeffect, and catalyst activity. See Catalyst Developmentwww.chem.cmuedu/groups/maty/about/research/05.html, hereby incorporatedby reference.

ATRP is considered to be one of the most successful CRP and has beenthoroughly described in a series of co-assigned U.S patents andapplications, such as U.S. Pat. Nos. 5,763,548; 5,807,937; 5,789,487;5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882; 6,407,187;6,512,060; 6,538,091; 6,541,580; 6,624,262; 6,624,263; 6,627,314;6,759,491; and U.S. patent application Ser. Nos. 09/534,827; 09/972,056;10/034,908; 10/269,556; 10/289,545; 10/638,584; 10/860,807; 10/684,137;10/781,061 and 10/992,249 all of which are herein incorporated byreference. ATRP has also been discussed in numerous publications withMatyjaszewski as co-author and reviewed in several book chapters. [ACSSymp. Ser., 1998, 685; ACS Symp. Ser., 2000; 768; Chem. Rev. 2001, 101,2921-2990; ACS Symp. Ser., 2003; 854; ACS Symp. Ser., 2006; 944.] Withinthese publications similar polymerization processes may be referred toby different names, such as transition metal mediated polymerization oratom transfer polymerization, but the processes may be similar and ifinvolve reaction mechanism of Scheme 1 will be referred to herein as“ATRP”. Such publications describe ATRP catalysts including the reducingpower of several transition metal ligand combinations and the manner inwhich an ATRP equilibrium can be adjusted for more or less reactivemonomers.

Embodiments of ATRP processes provide advantages over other CRPprocesses, including the availability wide variety of initiators andmacroinitiators, including wafers, inorganic colloids, glass, paper, andbio-active molecules including proteins, DNA, carbohydrates and manycommercial polymers may be simply synthesized as initiators; manypolymers produced by ATRP allow facile functionalization ortransformation of the end groups by replacing terminal halogens withazides, amines, phosphines and other functionalities via nucleophilicsubstitution, radical addition or other radical combination reactions;an abundance of monomers are polymerizable by ATRP. Such monomersinclude, but are not limited to, styrenics, (meth)acrylates,acrylonitrile, acrylamides, vinyl chlorides, and other monomers.Embodiments of ATRP allow the production of macromolecules with complextopology such as stars, combs and dendrimers, coupled with the abilityto control composition and hence functionality in block, gradient,periodic copolymers etc. and even control polymer tacticity. ATRP may becarried out in bulk, or in the presence of organic solvents or in waterunder homogeneous or heterogeneous conditions, in ionic liquids, and insupercritical CO₂.

However, for certain applications and economic considerations, a lowconcentration of transition metal catalyst in an ATRP medium may bedesired. Several methods have been developed to remove or reduce theamount of transition metals in the process, but these processes may addadditional cost to the preparation of polymers by ATRP.

Several methods may be used to provide polymers by ATRP processes withlow concentrations of catalysts. Such methods include performing an ATRPprocess with highly active catalyst that may require a lowerconcentration of catalyst to maintain the desired polymerization rate,for example, CuBr complexed by Me₆TREN is ˜10,000 more active than CuBrcomplexed by bipyridine ligands; immobilizing the catalysts on solidssuch as a hybrid catalyst system comprising both immobilized catalystcomplexes interacting with small concentrations of soluble catalysts(˜10-20 ppm); and several post polymerization methods developed torecover and regenerate catalysts, including separating the catalyst byfiltration, adsorption, precipitation or extraction. For example,CuBr/PMDETA complex may be oxidized to Cu(II) species by exposure to airand quantitatively extracted from toluene to water, resulting, in somecases, with less than 1 ppm of catalyst remaining in the polymer. Inspite of these advances, there remains a need to reduce theconcentration of catalyst in the active polymerization media whilemaintaining polymer reaction rate and retaining control over MW and PDI.

The most attractive route may be just a simple decrease of the amount ofthe catalyst, providing that it has a sufficient reactivity. Forexample, ATRP processes comprising CuBr/Me₆TREN complexes may be carriedout at room temperature with much lower concentrations of the copperbased catalyst. Regrettably, the amount of transition metal catalyst,such a Cu(I), may not simply be reduced 10,000 fold. Radical terminationreactions result in an increase in the concentration of the transitionmetal catalyst in the deactivator state and irreversible consumption ofthe catalyst activators. In certain embodiments with certain monomers,the polymerization may stop if the amount of Cu(I) present in thereaction is below 10% of the initiator (as, 1˜10% of chains areterminated). The amount of terminated chains depends on theconcentration of propagating radicals and rate constant of terminationaccording to equation 1, which describes the number of terminated chains(or loss of Cu(I) activator) in an ATRP.

−Δ[Cu^(I) ]=Δ[P _(t) ]=k _(t) [P ^(•)]² t  (1)

The ATRP rate law (Equation 2) indicates that the polymerization ratedepends on the ratio of Cu(I) to X—Cu(II) concentration but does NOTdepend on the absolute concentration of copper complexes. Thus, inprinciple, the amount of copper may be reduced without affectingpolymerization rate as long as the ratio of activator to deactivator ismaintained.

$\begin{matrix}{R_{p} = {{{k_{p}\lbrack M\rbrack}\lbrack P^{*} \rbrack} = {{k_{p}\lbrack M\rbrack}{K_{eq}\lbrack I\rbrack}_{o}\frac{\lbrack {Cu}^{I} \rbrack}{\lbrack {X - {Cu}^{II}} \rbrack}}}} & (2)\end{matrix}$

Unfortunately, as the reaction progresses the ratio of Cu(I) to X—Cu(II)is reduced through termination reactions and the polymerization ratedecreases and eventually, in the absence of a sufficient concentrationof the catalyst activator ATRP stops. See Equation 3. Thus, the amountof copper catalyst complexes that have generally been added to an ATRPreaction has exceed that of the expected number of terminated chains(i.e.>10% [I]₀) in order to drive the reaction to completion.

−Δ[Cu^(I) /L]=Δ[Cu^(II) X/L]=Δ[P _(dead) ]=k _(t) ∫[P ^(•)]² dt  (3)

Some amount of the deactivation species (i.e. X—Cu(II)) is also neededin the system for a well-controlled polymerization because molecularweight distribution and initial molecular weight depend on the ratio ofpropagation and deactivation rate constants and concentration ofdeactivator, according to Equation 4.

$\begin{matrix}{\frac{M_{w}}{M_{n}} = {1 + \frac{1}{{DP}_{n}} + {( \frac{\lbrack {R - X} \rbrack_{o}k_{p}}{k_{da}\lbrack {X - {Cu}^{II}} \rbrack} )( {\frac{2}{p} - 1} )}}} & (4)\end{matrix}$

In a RAFT polymerization process termination reactions are suppressedthrough the addition of a suitable thiocarbonylthio compound, also knownas a dithioester, to an otherwise conventional free radicalpolymerization; i.e. there is a continuous slow generation of radicalsby decomposition of a standard radical initiator in order to drive thereaction forward. Control in such a RAFT process is thought to beachieved through a degenerative chain transfer mechanism in which apropagating radical reacts with the thiocarbonylthio compound to producean intermediate radical species. This process decreases theinstantaneous number of free radicals available for terminationreactions that require two free radicals. RAFT (co)polymerizationreactions have been discussed in U.S. Pat. Nos. 6,153,705; 6,380,355;6,642,318 and 6,855,840.

There is a need for a transition metal catalyzed chain transferpolymerization process for free radically (co)polymerizable monomersthat uses low concentrations of catalysts.

SUMMARY

Polymerization processes of the present invention comprise low catalystconcentration. Embodiments include a polymerization process comprisingpolymerizing free radically (co)polymerizable monomers in apolymerization medium comprising one or more radically (co)polymerizablemonomers, a transition metal catalyst complex capable of participatingin a one electron redox reaction with an ATRP initiator; a free radicalinitiator; and an ATRP initiator; (wherein the concentration oftransition metal catalyst complex in the polymerization medium is lessthan 100 ppm). Further embodiments include a polymerization process,comprising polymerizing one or more radically (co)polymerizable monomersin the presence of at least one transition metal catalyst complex; anATRP initiator; and a reducing agent; wherein the transition metalcatalyst complex is present at less than 10 mole compared to the molesof radically transferable atoms or groups present on the ATRP initiator.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a graph of the kinetic data for an embodiment of apolymerization process comprising polymerizing styrene in the presenceof 15 ppm of copper with a polymerization medium having the followingcomponents, ratios, and conditions:St/EtBrIB/Cu(II)/Me₆TREN/Sn(EH)₂=200/1/0.003/0.1/0.1; [St]₀=5.82 M,T=110° C., in anisole (0.5 equivalents vs. monomer);

FIG. 2 is a graph of the molecular weight and polydispersity of apolystyrene formed as a function of conversion formed in the embodimentof FIG. 1;

FIG. 3 is a graph showing the evolution of molecular weight by GPCtraces during the embodiment of the polymerization process of FIG. 1;

FIG. 4 is a graph of the evolution of molecular weight andpolydispersity of polystyrene as a function of conversion in an ARGETATRP process comprising polymerizing styrene in the presence of 10 ppmof copper with a polymerization medium having the following components,ratios, and conditions:St/EtBrIB/Cu(II)/Me₆TREN/Sn(EH)₂=1000/1/0.003/0.1/0.1; [St]₀=5.82 M,T=110° C., in anisole (0.5 equivalents vs. monomer);

FIG. 5 is a graph of the evolution of molecular weight by GPC tracesduring the embodiment of the polymerization process of FIG. 4;

FIG. 6 is a graph of the GPC curves showing the presence of a smallamount of terminated polymer chains which were initiated by radicalsproduced from thermal decomposition of AIBN at beginning of activationprocedure before being overwhelmed by the bulk of the polymer preparedby CRP;

FIG. 7 is a graph of showing the temperature dependence of theconditional stability constant of Cu^(II)L ATRP catalysts with variousligands including TPMA, Me₆TREN, and PMDETA;

FIG. 8 is graphs of the kinetic data (8 a) and molecular weight andM_(w)/M_(n) data (8 b) as a function of conversion in an embodiment ofICAR ATRP process comprising styrene with 50 ppm and 1 ppm of Cu and thefollowing reaction conditions:St/EtBrIB/CuCl₂/Me₆TREN/AIBN=200/1/0.01/0.01/0.1;St/EtBrIB/CuCl₂/TPMA/AIBN=200/1/0.0002/0.1/0.1 [St]₀=5.82 M, 60° C., 50%anisole by volume (entries 1 & 10, Table 4);

FIG. 9 is a graph of data from a Predici computer simulation of firstorder kinetic plot for embodiments of ICAR ATRP processes comprisingstyrene, various ligands including TPMA, PMDETA, or bpy, and 50 ppm ofCu;

FIG. 10 is a graph of data from a Predici computer simulation of themolecular weight and polydispersity evolution in embodiments of ICARATRP processes comprising styrene, various ligands including TPMA,PMDETA, or bpy, and 50 ppm of Cu;

FIG. 11 is graph of the kinetic data from Predici computer simulationsfor embodiments of ICAR ATRP processes comprising styrene, variousligands including TPMA, PMDETA, or bpy, 50 ppm of Cu, and AIBN as thefree radical initiator;

FIG. 12 are graphs of data from Predici computer simulations of the ICARATRP homopolymerization process comprising MMA (6E-20 of St) with thefollowing polymerization conditions: Monomer: Initiator: Cull:AIBN=200:1:0.01:0.1, [Monomer]=6 M;

FIG. 13 are graphs of data from Predici computer simulations of the ICARATRP homopolymerization process comprising MMA and 20% styrene under thefollowing polymerization conditions: Monomer: Initiator: Cull:AIBN=200:1:0.01:0.1, [Monomer]=6 M;

FIG. 14 is a graph of the pH Dependence of the conditional stabilityconstant of Cu^(II)L ATRP catalysts;

FIG. 15 are graphs of the kinetic data (15 a) and molecular weight andMw/Mn data (15 b) as a function of conversion of an embodiment of aCuCl₂/TPMA mediated ARGET ATRP of BA, variable N₂H₄ reducing agent.[BA]₀:[EtBrIB]₀:[CuCl₂]₀:[TPMA]₀:[N₂H₄]₀=200:1.28:0.01:0.1:0.05 or 0.1;[BA]₀=5.88 M; 60° C., 20% anisole by volume;

FIG. 16 are graphs of the kinetic data of two embodiments of apolymerization process wherein CuCl₂/TPMA (16 a) and CuCl₂/Me₆TREN (16b) are transition metal catalysts in ARGET ATRP of BA with N₂H₄ as thereducing agent in different concentrations under the followingpolymerization conditions[BA]₀:[EtBrIB]₀:[CuCl₂]₀:[Ligand]₀:[N₂H₄]₀=200:1:0.01:0.1:0.05, 0.1 or1.0; [BA]₀=5.88 M; 60° C., 20% anisole by volume;

FIG. 17 illustrates ARGET ATRP of styrene with glucose as reducing agentin the presence of excess base: 17 a) triethylamine and 17 b)1,4-di-tert-butyl-pyridine (DBPyridine);

FIG. 18 a illustrates ARGET ATRP of styrene with glucose as reducingagent in the presence of excess ligand and FIG. 18 b illustrates SECtraces of polymers formed during polymerization with 10 ppm Cu(II);

FIG. 19 are semilogarithmic kinetic plots (19 a) and a graph of thedependence of molecular weights (closed symbols) and molecular weightdistributions (open symbols) (19 b) for ATRP of styrene andacrylonitrile;

FIG. 20 Evolution of SEC traces for ATRP of styrene and acrylonitrilewith Me₆TREN as a ligand (Table 13a, entry 1);

FIG. 21 are graphs of the kinetic data for an embodiment of an ARGETATRP of styrene and acrylonitrile with 10 ppm, 30 ppm, and 50 ppm ofcopper, under the following polymerization conditionsSt/AN/EBiB/Me₆TREN/Sn(EH)₂=600/390/1/0.5/0.5, in anisole at 80° C.;

FIG. 22 are graphs of the molecular weight and molecular weightdistribution as a function of conversion in ARGET ATRP of styrene andacrylonitrile with 10 ppm, 30 ppm, and 50 ppm of copper, under thefollowing polymerization conditionsSt/AN/EBiB/Me₆TREN/Sn(EH)₂=600/390/1/0.5/0.5, in anisole at 80° C.;

FIG. 23 are SEC curves showing the evolution of molecular weightdistribution during ARGET ATRP of styrene and acrylonitrile with 30 ppmof copper, under the following polymerization conditions:St/AN/EBiB/CuCl₂/Me₆TREN/Sn(EH)₂=600/390/1/0.03/0.5/0.5, in anisole at80° C.;

FIG. 24 are graphs of the kinetic data (24 a), molecular weight andmolecular weight distribution (24 b) as a function of conversion forARGET ATRP of styrene and acrylonitrile with 30 ppm of copper, under thefollowing polymerization conditions:St/AN/EBiB/CuCl₂/Me₆TREN/Sn(EH)₂=1000/650/1/0.05/0.5/0.5, in anisole;and

FIG. 25 illustrates the GPC traces for samples taken during thepreparation of high molecular weight polyacrylonitrile.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The present invention is directed to a polymerization process thatregenerate the transition metal in the activator state. Embodimentscould be considered to provide a new mechanism for Controlled RadicalPolymerization. Embodiments of the ATRP polymerization process comprisea transition metal complex catalyzed halogen transfer polymerizationwhere the transition metal complex is continuously reactivated byreaction with radicals. The radicals may be formed by the decompositionof a free radical initiator or by self initiation reactions.

In one embodiment the present invention could be considered to be a newmechanism for continuous reactivation a transition metal complexcatalyzed (pseudo)halogen transfer polymerization where the transitionmetal complex is continuously reactivated by reaction with formedradicals. This mechanism comprises initiators for continuous activatorregeneration (“ICAR”), see Scheme 2.

Embodiments of the present invention provide control over radicalreactions that may be considered conceptually to combine aspects of ATRPand RAFT. In RAFT, a chain transfer agent is employed to reversiblytransfer a labile dithioester end group among propagating radicalchains. Embodiments of ICAR ATRP process may be considered to besimilar, wherein the role of the dithioester transfer agent in RAFT isreplaced in ICAR by the initiator or growing polymer chain end in thepresence of low concentrations, ppm amounts, of an ATRP catalyst complexand there is a continuous slow generation of radicals by decompositionof a standard radical initiator in order to drive the reaction forward.Control in a RAFT process is thought to be achieved through adegenerative chain transfer mechanism in which a propagating radicalreacts with the thiocarbonylthio compound to produce an intermediateradical species. This process decreases the instantaneous number of freeradicals available for termination reactions that require two freeradicals. RAFT (co)polymerization reactions have been discussed in U.S.Pat. Nos. 6,153,705; 6,380,355; 6,642,318 and 6,855,840. This processmay be correlated to the process of scheme 2, where the transfer of aradically transferable atom is catalyzed by a transition metal complexand the reaction is driven by the presence of radicals formed bydecomposition of a free radical initiator.

The advantage of an ATRP process over a RAFT polymerization include theavailability of monofunctional and multifunctional ATRP initiators asdisclosed in other patents and patent applications with Matyjaszewski asinventor; the exchange reaction in an ATRP process is with a smallmolecule, (Mt(II) X), not with a polymeric chain end as in RAFT; and thedormant chain end can be readily modified to provide the desiredtele-functional groups. Although the invention is exemplified with ahalogen a transferable atom or group and copper based transition metalcomplexes, ATRP process may comprise any radically transferable atom orgroup and transition metal such as, for example, environmentallyfriendly iron complexes.

Embodiments of the polymerization process of the present invention aredirected towards polymerizing free radically (co)polymerizable monomersin the presence of a polymerization medium comprising at least onetransition metal catalyst, or precursor of the active catalytic species,at least one of a free radical initiator and a reducing agent, and anATRP initiator (RX). ATRP initiators include molecules comprising atleast one radically transferable atom or group, including small moleculeinitiators, polymeric initiators, and polymers in the polymerizationmedium comprising a dormant chain end that may be reinitiated orreactivated. The polymerization medium may initially comprise a freeradical initiator or a reducing agent or the free radical initiator orreducing agent may be added after initiation of the polymerization.After initiation of the polymerization of the radically(co)polymerizable monomers, free radical initiators or reducing agentmay be added continuously, sequentially, or all at once into thereaction medium.

In one embodiment, the ATRP process comprises polymerizing freeradically polymerizable monomers in a polymerization medium comprisingradically polymerizable monomers, a transition metal catalyst, an ATRPinitiator, a free radical initiator, wherein the concentration of thetransition metal catalyst complex in the polymerization medium is lessthan 100 ppm. The polymerization medium may further comprise a solvent,or water forming either a homogeneous or heterogeneous polymerizationmedium. The free radical initiator may be any molecule that may beinduced to form free radicals, such as a molecule that forms radicals bythermal, photoinitiated or other decomposition process. Free radicalinitiators include peroxides, azo compounds, disulfides, and tetrazines.More specifically, free radical initiators include acyl peroxides, acylperoxides, benzoyl peroxides, alkyl peroxides, cumyl peroxides, tributylperoxides, hydroperoxides, cumyl hydroperoxide, tibutyl hydroperoxide,peresters, tibutyl perbenzoate, alkyl sulfonyl peroxides, dialkylperoxydicarbonates, diperoxyketals, ketone peroxides, 2,2′azobisisobutyronitrile (“AIBN”), 2,2′ azobis (2,4-dimethylpentanenitrile), and 1, azobis (cyclohexane-carbonitrile). Additionally,some monomers may decompose to form radicals, such as styrene andstyrene derivatives, therefore the monomer of the polymerization processmay also act as the free radical initiator or reducing agent inembodiments of low catalyst ATRP processes. Free radical initiatorsdecompose to form radicals at different rates based on the decompositionstimulus, such as temperature. In certain embodiments, the free radicalinitiator may be soluble in the polymerization medium.

In certain embodiments, the free radical initiator is selected such thatat the temperature of the polymerization reaction the free radicalinitiator decomposes at a rate that is substantially the same as therate of termination in the polymerization. The free radical initiatorforms free radicals, or the equivalent of free radicals in the reactionmedium. See Table 1 for half lives of free radical initiators at varioustemperatures.

TABLE 1 HALF-LIVES OF FREE RADICAL INITIATORS^(a,b) Half-Life atInitiator 50° C. 60° C. 70° C. 85° C. 100° C. 115° C. 130° C. 145° C.155° C. 175° C. Azobisisobutyronitrile   74 hr 4.8 hr  7.2 min Benzoylperoxide 7.3 hr 1.4 hr 19.8 min Acetyl peroxide  158 hr 8.1 hr 1.1 hrLauryl peroxide 47.7 hr 12.8 hr 3.5 hr  31 min t-Butyl peracetate  88 hr12.5 hr 1.9 hr  18 min Cumyl peroxide  13 hr 1.7 hr 16.8 min t-Butylperoxide  218 hr  34 hr 6.4 hr 1.38 hr t-Butyl hydroperoxide  338 hr44.9 hr 4.81 hr ^(a)Data from Brandrup and Immergut [1989] and Huyser[1970]. ^(b)t½ values are for benezene or toluene solutions of theinitiators.

The system therefore behaves essentially as a conventional RP withsimilar kinetics but with the ATRP initiator acting as a combination“transfer agent”-initiator present at 50 ppm or less, in somepolymerization processes less than 10 ppm, Mt(II) or Mt(I) as a transfercatalyst.

In another embodiment, the polymerization process comprises polymerizingfree radically polymerizable monomers in a polymerization mediumcomprising radically polymerizable monomers, a transition metalcatalyst, an ATRP initiator, and a reducing agent. The polymerizationmedium may further comprise a solvent, or water. In such an embodiment,the transition metal complex may be initially in the oxidatively stablehigher oxidation state, such as Cu^(II), and reduced to the activatorstate to initiate the polymerization process. Excess of reducing agentmay be added to remove low concentrations oxygen from the system.

The reducing agent may be any reducing agent capable of reducing thetransition metal catalyst from a higher oxidation state to a loweroxidation state, thereby reforming the catalyst activator state. Suchreducing agents include, but are not limited to, SO₂, sulfites,bisulfites, thiosulfites, mercaptans, hydroxylamines, hydrazine (N₂H₄),phenylhydrazine (PhNHNH₂), hydrazones, hydroquinone, food preservatives,flavonoids, beta carotene, vitamin A, α-tocopherols, vitamin E, propylgallate, octyl gallate, BHA, BHT, propionic acids, ascorbic acid,sorbates, reducing sugars, sugars comprising an aldehyde group, glucose,lactose, fructose, dextrose, potassium tartrate, nitrites, nitrites,dextrin, aldehydes, glycine, and transition metal salts. The reducingagent may further be capable of complexing with the transition metal,thereby becoming a ligand.

In a preferred embodiment, the reducing agent does not produce an acidafter reducing the transition metal complex from the higher oxidationstate to the lower oxidation state, such as hydrazine and phenylhydrazine. With hydrazines, and substituted hydrazines, the products ofoxidation are either nitrogen gas or organic in nature, compared toprevious exemplified ARGET systems which predominately employed metalreducing agents for the reduction process in bulk media. [Jakubowski,W.; Min, K.; Matyjaszewski, K. Macromolecules 2006, 39, 39-45.] Thereducing agent may also scavenge oxidants in the polymerization medium.In certain embodiments, the amount of reducing agent will be determinedby the total concentration of the oxidants in the polymerization medium,if any; the amount of termination reactions in the polymerization; andthe desired rate of the redox reaction. Typically, the reducing agentwill be present in the polymerization medium such that the molar ratioof reducing agent to ATRP initiator is less than 0.1, or in certainembodiments, less than 0.05.

As noted above similar rules for catalyst selection exist in ARGET ATRPas did in Several factors should be considered for catalyst selection inARGET ATRP.

First, the release of acid during the oxidation of certain reducingagents (as is the case with many organic reducing agents that can beemployed in ARGET ATRP, including sugars, phenols or thiophenols,ascorbic acid, etc.) can destabilize copper-based ATRP catalysts derivedfrom amines. Therefore the addition of excess base, or excess ligand orreducing agent acting as a base, will likely be required to trap theacid. The addition of a base may modify the reducing power of thereducing agent. Of course, in the presence of acidic compounds (I.e., insome embodiments of ARGET ATRP), the stability of the complexes dependsvery strongly upon the basicity of the ligands. A ligand that is notvery basic (such as some of the heterodonor ligands) may beadvantageous.

Second, the basicity/nucleophilicity of the reducing agent such as N₂H₄and PhNHNH₂ may be an issue, particularly in the ARGET ATRP of styrene.The alkyl halide chain end may react with bases resulting in both in aloss of functionality and a consumption of reducing agent.

Third, the dynamics of the redox process between the Cu complexes andreducing agents (and ultimately attainable control) will likely dependupon the ligand used to form the complex with the catalyst (and value ofK_(ATRP)) that is employed.

In certain embodiments, the reducing agent may be select for aparticular polymerization process such that at the polymerizationtemperature the reducing agent reduces a sufficient quantity oftransition metal catalyst in the higher oxidation state to transitionmetal catalyst in the lower oxidation state to substantially maintainthe polymerization rate. For example, at the polymerization temperaturethe reducing agent reduces the additional amount of transition metalcatalyst in the higher oxidation state to substantially maintain theratio of transition metal catalyst in the higher oxidation state totransition metal catalyst in the lower oxidation state. To substantiallymaintain such ratio means that the ratio does not vary greater than 20%after initiation of the polymerization.

In embodiments of the polymerization process, such as ICAR ATRP andARGET ATRP polymerization processes, the concentration of the transitionmetal catalyst must be present in the polymerization medium and may beless than 100 ppm, less than 50 ppm, or even less than 10 ppm. Incontrast to the free radical initiators, the reducing agents do notinitiate a new polymer chain after reducing the transition metalcatalyst in the higher oxidation state.

In embodiments of the ATRP process, the atom or group transfertransition metal complex may be an efficient deactivator, i.e.efficiently donate the (X) atom or group to the growing active chain.The process will be initially exemplified by the use of a very smallamount of Cu, ˜10 ppm complexed with a ligand that forms an active ATRPcatalyst and is also an effective deactivator, such astris[2-(dimethylamino)ethyl]amine (“Me₆TREN”),tris[(2-pyridyl)methyl]amine (“TPMA”), and H₆TREN. Other embodimentsinclude ligands forming less active catalysts such asN,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA),4,4′-di-(5-nonyl)-2,2′-dipyridyl (dNbpy) andN-(n-octyl)-2-pyridylmethanimine.

The use of low concentrations of catalyst in an ATRP reaction reducesthe impact of catalyst based side reactions that limited the ability toprepare high molecular weight materials in some embodiments. Onepossible explanation of this limitation may be that the radicalsinteracted with the catalyst complex. For example, the polystyrylradical may be oxidized to a cation by the Cu^(II) species, therebylimiting formation of well-defined high molecular weight polystyrenes byATRP. However, since this ICAR ATRP and ARGET ATRP may comprise verysmall amounts of transition metal in the deactivator state, thesynthesis of high molecular weight polymers for all monomers are nowmuch more feasible. In certain embodiments of the polymerizationprocesses of the present invention, excess ligand may be added to thepolymerization. Excess ligand is present when the quantity of ligandpresent in the polymerization medium exceeds the amount of ligandrequired to complex with the transition metal to form the transitionmetal catalyst. One skilled in the art would understand the coordinationcharacteristics of each transition metal complex. The amount of excessligand, or ligand surrogate such as free amine, may be as much as tentimes the require amount of ligand. In some polymerization processeslower amounts of ligand may lead to polymers with higherpolydispersities. At reduced quantities of ligand the transition metalcatalyst may complex with the monomer. The ligand may complex with themonomer such as styrene with other components of the polymerizationmedium. For example, if tin is used as a reducing agent, sufficientligand should be added to allow for complex formation with both thereducing agent and the transition metal of the catalyst.

The present invention is also directed to polymers comprising highmolecular weight. Embodiments include polystyrene comprising end groupstypical of an ATRP process and a molecular weight of greater than 50,000and polyacrylonitrile comprising end groups typical of an ATRP processand a molecular weight of greater than 50,000. In ATRP processes, theinitiator is of the formula R—X, where X is the radically transferableatom or group. After polymerization, a typical polymer formed by ATRPwill have the R group on one end and the X group on the other end. Thedefinitions of R and X are defined in United States patents that areincorporated by reference.

In certain embodiments of an ICAR ATRP or ARGET ATRP process, the freeradical initiator or the reducing agent controls the rate ofpolymerization by regenerating the activator catalyst complex whileallowing sufficient amounts of the catalyst complex efficientlydeactivates the growing chains to remain. In such embodiments,controlled synthesis (M_(w)/M_(n)<1.2) of polystyrene and poly(alkyl(meth)acrylates) can be performed with catalyst concentrations between 1and 50 ppm. At such concentrations, catalyst removal or recycling may beunnecessary for many industrial applications, since the color ofproducts are not significantly affected by the such low concentrationsof catalysts.

Furthermore, because some of the components of the ATRP equilibrium arenot oxidatively stable, special handling procedures are often requiredto remove all oxidants from the system. Embodiments of the ICAR ATRP andARGET ATRP process comprise initial use of the oxidatively stablecatalyst precursors that can be prepared, stored, and shipped for use inATRP. The transition metal complex in the activator state may begenerated in situ from free radical initiators, a reducing agent, an insitu formed peroxide in the case of acrylate polymerization, or acombination thereof [Acar, A. E.; Yagci, M. B.; Mathias, L. J.Macromolecules 2000, 33, 7700-7706] and the oxidatively stabletransition metal catalyst, for example Cu^(II) or Fe^(II).

In certain embodiments, the free radical initiator slowly andcontinuously decomposes to prevent the build up of the persistentradical, or higher oxidation state transition metal complex, formed bytermination reactions. This decomposition of the free radical initiatormay be used to maintain a substantially constant rate of polymerization;i.e. keep the ratio of transition metal in the low oxidation state(activator state) to transition metal in the higher oxidation state(deactivator state) relatively constant. In other embodiments, the freeradical initiator or reducing agent may be used to increase or decreasethe polymerization rate.

In other embodiments, the ATRP polymerization process comprises twodifferent free radical initiators. For example, one free radicalinitiator may quickly activate the catalyst complex to ensure rapidinitiation of the polymerization and the other may slowly act throughoutthe reaction to reactivate the complex, for example. The self-formedfree radical initiator such as present in nitroxide mediatedpolymerizations with styrene and TEMPO may also be used. [Georges, M.K., Veregin, R. P. N., Kazmaier, P. M., Hamer, G. K.; Macromolecules 26:2987-2988, 1993.] Free radical initiators may be used in coordinationwith reducing agents, also.

The following examples exemplify the broad applicability of this novelCRP. In order to obtain consistent kinetics the reagents used in most ofthe examples were purified however as detailed in some examples this isnot a requirement and the reaction can be conducted directly withindustrial grade monomers and in the presence of low concentrations ofoxygen.

EXAMPLES

Chemicals. Styrene (St) (Aldrich, 99%) and n-butyl acrylate (nBA) (Acros99+%) were passed through a column filled with neutral alumina, driedover calcium hydride, and distilled under reduced pressure.Tris(2-(dimethylamino)ethyl)amine (Me₆TREN) was synthesized followingpreviously reported procedure. Ethyl 2-bromoisobutyrate (EtBrIB) (Acros,98%), copper(II) chloride (Acros, 99%), tin(II)2-ethylhexanoate(Sn(EH)₂) (Aldrich), anisole (Aldrich, 99%) were used as received.

In order to obtain consistent kinetics, the reagents used in most of theexamples were purified, however as detailed in some examples this is nota requirement and the reaction can be conducted directly with industrialgrade monomers.

Analysis. Molecular weight and polydispersity were determined by gelpermeation chromatography (GPC). The GPC was conducted with a Waters 515pump and Waters 2414 differential refractometer using PSS columns(Styrogel 10⁵, 10³, 10² Å) in THF as an eluent at 35° C. and at a flowrate of 1 mL/min. Linear polystyrene standards were used forcalibration.

Conversion of styrene were determined using a Shimadzu GC 14-A gaschromatograph equipped with a FID detector using a J&W Scientific 30 mDB WAX Megabore column and anisole as an internal standard. Injector anddetector temperatures were kept constant at 250° C. Analysis was carriedout isothermally at 60° C. for 2 min followed by an increase oftemperature to 140° C. at a heating rate of 40° C./min and holding at140° C. for 2 min Conversion was calculated by detecting the decrease ofthe monomer peak area relative to the peak areas of the standards.

Comparative Examples

Table 2 is shows typical ratio's of reagents used various ATRP processesand in a RAFT polymerization process.

TABLE 2 Typical molar ratios of reagents used in various ATRP processesand a RAFT process Polymerization R-X Reducing method M X = Br, ClCu^(I)X Cu^(II)X Ligand agent AIBN Normal ATRP 200 1 1 — 1 — — ReverseATRP 200 — — 1 1 — 0.5 SR&NI ATRP 200 1 — 0.2 0.2 — 0.1 AGET ATRP 200 1— 0.2 0.2 0.18 — ARGET ATRP 200 1 — <0.01 0.1 0.1  — ICAR ATRP 200 1 —<0.01 0.01 — <0.1  RAFT 200 1 dithioester — — — — 0.1

As shown in Table 2 significantly less transition metal complex istypically comprised in ARGET ATRP and ICAR ATRP processes than the otherlisted ATRP process. While similar reagents are used in simultaneousreverse and normal initiation (“SR&NI”) ATRP as in ICAR ATRP, ICAR ATRPallows the advantage of the use of much lower concentrations oftransition metal catalysts. For more description of SR&NI ATRP, see U.S.Pat. No. 6,759,491.

The following examples show that a controlled radical polymerization ispossible with low levels of transition metal catalysts, or catalytichalogen transfer agents, providing polymers with known chain endfunctionality. PREDICI simulations were conducted on embodiments of ICARATRP and ARGET ATRP process and the simulations confirmed applicabilityof the process parameters and provided further understanding of theparameters of the process.

In the following examples, the polymerization of styrene with 5 ppm ofCuCl₂/Me₆TREN and 500 ppm of Sn(EH)₂ resulted in the formation ofessentially colorless high molecular weight polystyrene withM_(n)=12,500 (M_(n,th)=12,600) and M_(w)/M_(n)=1.28. When thepolymerization was carried out with 1 ppm of CuCl₂/Me₆TREN, themolecular weight of the resulting polymer was still well controlledM_(n)=7200 (M_(n,th)=9,000) but polydispersities were higher,M_(w)/M_(n)=1.64. The polymerization of n-butyl acrylate was conductedwith 50 ppm of CuCl₂/Me₆TREN and 500 ppm of Sn(EH)₂ forming poly(butylacrylate) with M_(n)=19,400 (M_(n,th)=18,100) and M_(w)/M_(n)=1.26.

These examples show that a controlled radical polymerization is possiblewith low levels of transition metal catalysts, or catalytic halogentransfer agents, providing polymers with known chain end functionality.

Example 1 General Procedure for Activators ReGenerated by ElectronTransfer (“ARGET”) ATRP of Styrene (with Number Average Degree ofPolymerization (DP_(n)) of 200 and at 50 ppm of Cu)

Degassed styrene (5.0 ml, 44 mmol) and anisole (1.5 ml) were transferredvia degassed syringes to dry, thoroughly purged by flushing withnitrogen Schlenk flask. Next, CuCl₂ (0.29 mg, 0.22×10⁻² mmol)/Me₆TREN(0.57 0.22×10⁻² mmol) complex in degassed anisole (0.5 ml) was added.Mixture was stirred for 10 minutes and then purged solution of Sn(EH)₂(7.0 μl, 2.2×10⁻² mmol) and Me₆TREN (5.7 μl, 2.2×10⁻² mmol) in anisole(0.5 ml) was added. At the end EtBrIB (32.1 μl, 21.9×10⁻² mmol)initiator was added. An initial sample was taken and the sealed flaskwas placed in thermostated oil bath at 110° C. The samples were taken attimed intervals and analyzed by gas chromatography and gel permeationchromatography. The polymerization was stopped after 7.6 h by openingthe flask and exposing the catalyst to air. M_(n, GPC)=12700,M_(w)/M_(n)=1.11, conversion=59%.

Example 2 General Procedure for ARGET ATRP of Styrene Under Air(DP_(n)=200, 50 Ppm of Cu)

Styrene (5.0 ml, 44 mmol) and anisole (1.5 ml) were added to openSchlenk flask. Next, CuCl₂ (0.29 mg, 0.22×10⁻² mmol)/Me₆TREN (0.57 μl,0.22×10⁻² mmol) complex in anisole (0.5 ml) was added. Mixture wasstirred for 10 minutes and then solution of Sn(EH)₂ (7.0 μl, 2.2×10⁻²mmol) and Me₆TREN (1.7 μl, 0.7×10⁻² mmol) in anisole (0.5 ml) was added.At the end EtBrIB (29.7 20.3×10⁻² mmol) initiator was added. Next,Schlenk flask was closed sealed and, after taking initial sample, placedin thermostated oil bath at 110° C. The samples were taken at timedintervals and analyzed by gas chromatography and gel permeationchromatography. The polymerization was stopped after 20 h(M_(n, GPC)=15900, M_(w)/M_(n)=1.28, conversion=76%) by opening theflask and exposing the catalyst to air.

Example 3 Preparation of Block Copolymers: PS-PnBA and PnBA-PS

An embodiment of ARGET ATRP was used for preparation of blockcopolymers. Copolymers PS-PnBA styrene and PnBA-PS were synthesizedusing previously specified conditions for polymerization of styrene(WJ-03-27) and n-butyl acrylate (WJ-03-53) in the presence of reducingagent Sn(EH)₂. The conditions and results for all the reactions arepresented in Table 3. The polystyrene macroinitiator was prepared(WJ-03-55) by polymerization of styrene in the presence of 15 ppm of Cu.As in experiment WJ-03-27, a well controlled polymerization was observeddemonstrating that results are reproducible.

Polystyrene with Mw=16000 and PDI=1.18 was precipitated and then used asmacroinitiator in an ARGET ATRP of nBA (WJ-03-56). Chain extension of PSwith nBA was performed in the presence of 50 ppm of Cu species. Asexpected from the results on homopolymerization of nBA (WJ-03-53) thereaction was less controlled than with styrene, although molecularweights were close to theoretical values the PDI increased throughreaction from 1.18 to 1.33.

A similar synthetic strategy was used for preparation of PnBA-PS blockcopolymer. First PnBA macroinitiator was obtained (WJ-03-57) and thenchain extended by formation of a PS block (WJ-03-59). In this casepolymerization of nBA resulted in macroinitiator PnBA with Mw=17600 andPDI=1.32 (WJ-03-57) and since the polymerization of styrene is muchbetter controlled this resulted in a decrease in the PDI of the finalblock copolymer to 1.18 (WJ-03-59). In all reactions monomodaldistribution of MW was observed, molecular weights were close totheoretical values.

Polymerization of nBA at 10 ppm in the presence of reducing agentSn(EH)₂ was carried out. From the tables it can be seen that molecularweights were close to theoretical values and a PDI >1.50 was observed.

TABLE 3 Conditions and results for ARGET ATRP of Styrene andn-butylacrylate. Cu Time Conv. Label In [ppm] CuCl₂ Me₆TREN AIBN Sn(En)₂(min) (%) M_(n, theo) ^(b) M_(n, GPC) M_(w)/M_(n) WJ-03-27^(a) 1 150.003 0.1 — 0.1 1230 0.76 15250 17100 1.18 WJ-03-53^(c) 1 50 0.0078 0.1— 0.1 370 0.91 18100 19400 1.26 WJ-03-55^(a) EtBrIB 15 0.003 0.1 — 0.11180 0.77 15500 16000 1.18 WJ-03-56^(c) PS 50 0.0078 0.1 — 0.1 1260 0.5927800 26300 1.33 WJ-03-55 WJ-03-57^(c) EtBrIB 50 0.0078 0.1 — 0.1 2400.76 15200 17600 1.32 WJ-03-58^(c) EtBrIB 10 0.0016 0.1 — 0.1 520 0.9318600 18700 1.54 WJ-03-59^(a) PnBA 15 0.003 0.1 — 0.1 1845 0.88 3380032900 1.18 WJ-03-57 ^(a)[St]₀/[In]₀ = 200; [St]₀ = 5.82 M; T = 110° C.,in anisole (0.5 volume equivalent vs. monomer); ^(b)M_(n, theo) =([M]₀/[In]₀) × conversion ^(c)[nBA]₀/[In]₀ = 160; [St]₀ = 5.88 M; T =60° C., in anisole (0.2 volume equivalent vs. monomer);

TABLE 4 Experimental conditions and properties of PS prepared by ARGETATRP - effect of amount of copper.^(a) Molar ratios Cu Time Conv. EntrySt EtBrIB CuCl₂ Me₆TREN Sn(EH)₂ [ppm] (min) (%) M_(n, theo) ^(b)M_(n, GPC) M_(w)/M_(n) WJ-03-05 200 1 0.1 0.1 0.1 500 1020 67 1400017000 1.12 WJ-03-08 200 1 0.01 0.1 0.1 50 460 59 12300 12700 1.11WJ-03-27 200 1 0.003 0.1 0.1 15 1230 76 15300 17100 1.18 WJ-03-24 200 10.001 0.03 0.1 5 1440 45 9000 7200 1.28 WJ-03-28 200 1 0.0002 0.1 0.1 11230 63 12600 12500 1.64 WJ-03-14 1000 1 0.1 0.1 0.1 100 2630 69 6890071800 1.18 WJ-03-15 1000 1 0.01 0.1 0.1 10 1590 64 64000 63000 1.17^(a)[St]₀ = 5.82 M; T = 110° C., in anisole (0.5 volume equivalent vs.monomer); ^(b)M_(n, theo) = ([M]₀/[EtBrIB]₀) × conversion.

Discussion of Results

Several examples of an ATRP process comprising a reducing agent wereperformed and are summarized in Table 4. The concentration of thetransition metal catalyst was varied in the first four experiments. At 1ppm transition metal catalyst complex, CuCl₂/Me₆TREN, in thepolymerization medium, polystyrene was prepared with the characteristicsof a polymer prepared by a CRP process. The polymerization processesformed substantially colorless polystyrene.

FIG. 1 is a kinetic plot of data obtained during the ATRP polymerizationprocess comprising polymerizing styrene in the presence of 15 ppm of acopper/Me₆ TREN catalyst and a reducing agent Sn(EH)₂, and an ATRPinitiator, EtBrIB, wherein the Sn(EH)₂ corresponds to 10% of the ATRPinitiator (Tables 3 and 4, entry WJ-03-27). FIG. 1 shows that the rateof polymerization was constant with only a slight decrease after 500minutes. The molecular weight and PDI curves in FIG. 2 indicatesexcellent control over the polymerization process. FIG. 3 shows smoothshift of entire molecular weight distribution towards higher molecularweights. However when the concentration of transition metal catalyst, orcatalytic transfer agent, is reduced below 5 ppm of copper under theseconditions (or without Cu) uncontrolled polymerization is observed(Table 4, entry WJ-03-28). Note however that the reaction with 5 ppmtransition metal halogen transfer catalyst (Table 4, entry WJ-03-24)does produce a polymer with low PDI.

One of the limitations of ATRP is that unlike RAFT the reactions havenot been able to prepare very high molecular weight copolymers. Onepossible explanation is that the radicals could interact with thecatalyst complex. E.g. the polystyryl radical can be oxidized to acation by the Cu(II) species and this may be the main side reactionlimiting formation of well-defined high molecular weight polystyrenes byATRP. However, since the continuous activation process can now be runwith very small amounts of Cu(II) species the synthesis of highmolecular weight polystyrenes are now much more feasible. FIGS. 4 and 5demonstrate application of ARGET to formation of higher molecular weightpolystyrenes. The amount of Cu was reduced down to 10 ppm withpreservation of an appropriate level of control (Table 4, entryWJ-03-15). FIG. 5 illustrates some tailing towards lower molecularweight due to termination reactions, but overall control is stillexcellent.

When a stoichiometric amount of Me₆TREN to Cu was used, less control wasobserved. Only low molecular weight oligomers were formed (Table 5,entry WJ-03-06). This suggests changing of polymerization mechanismsfrom radical to cationic. It is possible that formed stronger Lewisacids SnCl₂(EH)₂ can catalyze a cationic process, it is also possiblethat they can undergo metathesis and generate even stronger Lewis acids;SnCl₄ or SnCl₃EH. These

TABLE 5 Experimental conditions and properties of PS prepared by ARGETATRP - effect of ligand.^(a) Molar ratios Cu Time Conv. Entry St EtBrIBCuCl₂ Me₆TREN Sn(EH)₂ [ppm] (min) (%) M_(n, theo) ^(b) M_(n, GPC)M_(w)/M_(n) WJ-03-08 200 1 0.01 0.1 0.1 50 460 59 12300 12700 1.11WJ-03-07 200 1 0.01 0.03 0.1 50 460 34 7100 6900 1.20 WJ-03-06 200 10.01 0.01 0.1 50 1000 44 9200 oligomers — ^(a)[St]₀ = 5.82M; T = 110°C., in anisole (0.5 volume equivalent vs. monomer); ^(b)M_(n, theo) =([M]₀/[EtBrIB]₀) × conversion. ^(a)[St]₀ = 5.82M; T = 110° C., inanisole (0.5 volume equivalent vs. monomer); ^(b)[St]₀ = 5.82M; T = 60°C., in anisole (0.5 volume equivalent vs. monomer); ^(c)[nBA]₀ = 5.88M;T = 60° C., in anisole (0.2 volume equivalent vs. monomer); ^(d)[St]₀ =5.82M; T = 110° C., in anisole (0.5 volume equivalent vs. monomer),reaction under air; ^(e)M_(n, theo) = ([M]₀/[EtBrIB]₀) × conversion.Lewis acids may also destroy the active Cu/Me₆TREN species by directcomplexation with the ligand. In certain embodiments, a small excess ofligand, or ligand surrogate, should be used.

The kinetic plot from the polymerization of styrene with 15 ppm ofcopper targeting DP=200 at two different temperatures 60 and 110° C.(Table 6, entry WJ-03-27 and WJ-03-46) indicates that the rate ofpolymerization is faster at 110° C., although both reactions are wellcontrolled.

A successful polymerization of n-butyl acrylate was also performed inthe presence of 50 ppm of copper. As expected, polymerization of theacrylate was much faster than for styrene at similar conditions (Table6, entry WJ-03-08 and WJ-03-53).

Cu(I)/Me₆TREN complexes are easily oxidized by air. However, theresulting Cu(II) species can be still regenerated to Cu(I) state by theaction of a reducing agent, such as Sn(EH)₂. Thus, in one experiment(Table 6, entry WJ-03-09 and WJ-03-13) no nitrogen purging was conductedbut an excess of Sn(EH)₂ was added to the reaction medium. A shortinduction period was observed but then polymerization started and goodcontrol over molecular weight and polydispersities was observed.

TABLE 6 Experimental conditions and properties of PS and PnBA preparedby ARGET ATRP - effect of monomer, temperature and air. Molar ratios CuTime Conv. Entry M EtBrIB CuCl₂ Me₆TREN Sn(EH)₂ [ppm] (min) (%)M_(n, theo) ^(e) M_(n, GPC) M_(w)/M_(n) WJ-03-27^(a) 200 1 0.003 0.1 0.115 1230 76 15300 17100 1.18 WJ-03-46^(b) 200 1 0.003 0.1 0.1 15 31500.24 4800 4500 1.18 WJ-03-08^(a) 200 1 0.01 0.1 0.1 50 460 59 1230012700 1.11 WJ-03-53^(c) 160 1 0.0078 0.1 0.1 50 370 91 18100 19400 1.26WJ-03-07^(a) 200 1 0.01 0.03 0.1 50 460 34 7100 6900 1.20 WJ-03-13^(d)200 1 0.01 0.03 0.1 50 1415 76 15200 15900 1.28 WJ-03-09^(d) 200 1 0.010.1 0.1 50 1380 75 15000 16200 1.45

The amount of transition metal catalyst complex species in ATRP can bereduced down to a few ppm without losing control of polymerization, ifan appropriate amount of reducing agent is used to account for oxidationof the catalyst as a result of terminated chains. There are severalrequirements for an efficient reaction in the presence of a reducingagent:

-   -   The redox process should occur without generation of initiating        radicals.    -   Reducing agent may also be involved in atom transfer process        (this would generate dual catalytic system, e.g. bimetallic        catalysis), however, the sufficient amount of quickly        deactivation species (i.e., X—Cu(II)) is needed for control.        Molecular weight distribution and initial molecular weight, both        depend on the ratio of propagation to deactivation rates,        according to equations: 2 and 3.    -   The position of equilibrium between reducing species and ATRP        true catalyst should allow for a sufficient amount of Cu(II)        species and sets the overall rate of ATRP.    -   The concentration of reducing agent should account for [Cu(II)]        sufficient amount of transition metal species to be activated,        amount of air or some other radical traps present in the system,        and the amount of terminated chains. When Sn(EH)₂ species are        used as the reducing agent this concentration is ˜50 ppm but        depends on the particular reaction conditions.

The minimal amount of active ATRP catalyst also depends on theparticular system, for styrene polymerization the transition metalcatalyst may be to a few ppm, significantly lower than in any otherreported ATRP process. The examples of ARGET ATRP detailed hereindemonstrate a significant improvement over traditional ATRP, since itcan be carried out with drastically reduced amount of Cu species and FDAapproved Sn(EH)₂ or other environmentally sound reducing agents (sugars,ascorbic acid).

Example 4 Development of Initiators for Continuous ActivatorRegeneration (ICAR) ATRP

In the set of examples described above the catalyst complex wasreactivated by addition of a reducing agent however other approaches,closer to present industrial practice for RP, for reactivation of thelower oxidation state transition metal complex have now been shown toalso work. The polymerization medium comprises a significantly lowercatalyst concentration, for example many times less than the totalnumber of polymer chains formed in the polymerization, in order that thereaction can continue the radical initiator has to continuously generateradicals at a rate comparable to radicals consumed by terminationreactions. The radicals can be formed by any reaction mechanisms.Indeed, as shown below, in the case of styrene polymerization this isthe mechanism that actually operates, but it was analysis of the aboveresults that led to this unexpected recognition.

From all previous data on ARGET ATRP of styrene it could be observed,that the overall rate of polymerization did not change with varyingamounts of Cu, ligand or Sn(EH)₂. Due to the high temperature (110° C.),which was used in all previous experiments, this indicated that the rateof polymerization was controlled by thermal production of radicals fromthe monomer. [Odian, “Principles of Polymerization” 4^(th) edition, page226] The rate of polymerization is controlled by thermal initiation ofstyrene. Styrene based radicals can form independently to reduce Cu(II)to Cu(I) and regenerate the active catalyst. Therefore polymerizationswere conducted with a low concentration of catalyst without the presenceof a reducing agent. The regeneration of Cu(I) activator species, whichcan be lost due to termination reactions (e.g. radical coupling), wasperformed by two different methods:

generation of radicals by thermal initiation from styrene monomer(polymerization at 110° C.)

generation of radicals by thermal decomposition of AIBN (polymerizationat 60° C.)\

In both cases, radicals are produced slowly throughout the reaction andare able to continuously reduce Cu(II) to Cu(I), so that the activatorcomplex was continuously regenerated. The conditions employed for theseinitial reactions and the results are presented in Tables 5-6. In firstexperiments (WJ-03-30, 31, 32), styrene was polymerized with 3 ppm ofadded Cu species and radicals were produced by thermal initiation ofstyrene. The results show that the reactions were not controlled and ahigh molecular weight product with high PDI was obtained. The relativelyuncontrolled character of the polymerization could be due to too low aconcentration of ligand, which allows the copper to be complexed bymonomer leading to loss of active metal catalyst complex (Cu(I)/ligand),as the ligand was involved in side reactions. Consequently, in next tworeactions (WJ-03-36, 37) amount of ligand was increased. Styrene waspolymerized in the presence of 50 and 5 ppm of Cu species respectively.CuCl₂/Me₆TREN was used as catalyst complex and ratio of In/Cu/ligand was1/0.01/0.1 and 1/0.001/0.1. The results showed that the polymerizationin the presence of 50 ppm Cu species was well controlled, molecularweights were close to theoretical values and low PDI (1.17) wasobserved. In reaction WJ-03-37 with only 5 ppm of Cu species much higherPDI (1.63) was observed and molecular weights were higher than thetheoretical values. This suggests that the concentration of radicals wasinitially too high and all of Cu(II) species were reduced to Cu(I). Thisleads to higher molecular weights since the amount of deactivator Cu(II)is too small to efficiently deactivate the growing polymer chains. Inorder too obtain controlled ATRP one should increase the effectiveamount of Cu(II) species in the system. This can be accomplished eitherby increasing the initial amount of Cu(II) species in the system or bydecreasing the temperature. At lower temperature less Cu(II) specieswill be reduced to Cu(I) since concentration of radicals produced in thethermal process will be lower.

In the next series of experiments (See Table 8) styrene was polymerizedwith 15 ppm of Cu species present in the reaction and radicals wereproduced by thermal decomposition of AIBN. In the first reactions(WJ-03-33, 34, 35) styrene was polymerized at 60° C. in the presence ofAIBN and/or reducing agent Sn(EH)₂. In experiment WJ-03-33 AIBN andSn(EH)₂ were used together. The polymerization was slow but low PDI(<1.4) was observed and MW were close to calculated values. The nextreaction, WJ-03-34, was performed only in the presence of Sn(EH)₂. Theresults shows that polymerization was relatively well controlled,molecular weigh is were close to theoretical values and low PDI (1.30)was observed but the rate of the reaction was slightly slower than theprevious one when AIBN and Sn(EH)₂ were used together. In reactionWJ-03-35 styrene was polymerized in the presence of AIBN without anyadded reducing agent. The polymerization was initially controlled butafter 20 h a bimodal distribution of MW could be observed. This could bedue to loss of active complex from the system due to complexation of theligand with the monomer, which is present in large excess compared tothe transition metal.

In the following set of experiments a higher amount of ligand was usedand the amount of AIBN added to the reaction was varied to increase therate of polymerization. CuCl₂/Me₆TREN was used as catalyst complex andthe ratio of In/Cu/ligand was 1/0.003/0.1 while the concentration ofAIBN was varied from 0.01 to 0.1 equivalents vs. initiator. In allreactions a monomodal distribution of MW was observed. Molecular weightswere close to theoretical values, but slightly higher PDIs (>1.4) wereobserved. Increasing the concentration of added AIBN from 0.01 to 0.1equivalents vs. ATRP initiator resulted in an increased rate ofpolymerization but reactions were still very slow.

Example 5 Polymerization of Styrene in the Presence of AIBN

ATRP with low catalyst concentration was performed without the presenceof added reducing agent. The regeneration of Cu(I) species, which can belost due to termination reactions (e.g. radical coupling), was performedby generation of radicals by thermal decomposition of AIBN(polymerization at 60° C.). In this case, radicals are produced slowlythrough whole reaction time and are able to reduce Cu(II) to Cu(I), sothat active complex can be regenerated. The conditions and results forall the reactions are presented in Table 9.

TABLE 8 Conditions and results for ATRP of St initiated by AIBN at lowcatalyst concentration^(a) Time Conv. Label EtBrIB Cu [ppm] CuCl₂Me₆TREN AIBN Sn(EH)₂ (min) (%) M_(n, theo) ^(b) M_(n, GPC) M_(w)/M_(n)WJ-03-27 1 15 0.003 0.1 — 0.1  1230 0.76 15250 17100 1.18 WJ-03-33 1 150.003 0.02 0.01 0.02 4635 0.19 3720 4100 1.36 WJ-03-34 1 15 0.003 0.02 —0.02 4600 0.12 2360 2590 1.30 WJ-03-35 1 15 0.003 0.003 0.01 — 4570 0.193560 37200 1.40 WJ-03-38 1 15 0.003 0.1 0.01 — 7200 0.26 5200 3800 1.51WJ-03-39 1 15 0.003 0.1 0.05 — 7200 0.28 5500 5100 1.44 WJ-03-40 1 150.003 0.1 0.1  — 7200 0.56 11200 9800 1.38 ^(a)[St]₀/[EtBrIB]₀ = 200;[St]₀ = 5.82M; T = 60° C., in anisole (0.5 volume equivalent vs.monomer); ^(b)M_(n, theo) = ([M]₀/[EtBrIB]₀) × conversion

TABLE 9 Conditions and results for ATRP of St initiated by AIBN at lowcatalyst concentration Time Conv. Label EtBrIB Cu [ppm] CuCl₂ Me₆TRENAIBN Sn(EH)₂ (min) (%) M_(n, theo) ^(b) M_(n, GPC) M_(w)/M_(n)WJ-03-40^(a) 1 15  0.003 0.1 0.1 — 7200 0.56 11200 9800 1.38 WJ-03-60 150 0.01 0.1 0.1 — 2760 0.40 8000 7600 1.19 CuCl WJ-03-61 1 50 0.01 0.10.1 — 2760 0.41 8200 7700 1.26 WJ-03-62 1 50 0.01 0.01 0.1 — 2760 0.448700 7900 1.12 ^(a)[St]₀/[EtBrIB]₀ = 200; [St]₀ = 5.82M; T = 60° C., inanisole (0.5 volume equivalent vs. monomer); ^(b)M_(n, theo) =([M]₀/[EtBrIB]₀) × conversion

In the last two experiments in Table 9 (Runs WJ-03-61 and 62) the amountof ligand, Me₆TREN, was varied with a constant concentration of 50 ppmof Cu present in the polymerization of styrene. The ratio ofIn:Cu:ligand in the first and second reactions were 1:0.01:0.01 and1:0.01:0.1 respectively. In reaction WJ-03-62 no excess of ligand wasused while in experiment WJ-03-61 the polymerization of styrene wasperformed in the presence of 10 fold excess of ligand. The molecularweights were close to theoretical values and low PDI was observed forboth runs. This suggests that no excess of ligand is needed since theexcess ligand could participate in side reactions and influence thefinal PDI. This is the contrary to the experience with ARGET ATRP wherean excess of ligand may be needed, due to possible complexation with thereducing agent Sn(EH)₂ or its products Sn(EH)₂Cl₂, SnCl₄.

In reactions WJ-03-60 polymerization of styrene was performed startingwith 50 ppm of the Cu(I) complex formed in the presence of excessligand. It can be seen that the results from this reaction are slightlyimproved compared to reaction where Cu(II) was used (WJ-03-61).Molecular weights were close to theoretical values and a lower PDI(<1.20) was observed.

There are two possible reasons for this result:

(i) The equilibrium between Cu(I) and Cu(II) species in the system mayform faster when Cu(I) species are used, and thus better control ofpolymerization can be obtained. When starting from Cu(II) species andusing AIBN to activate the polymerization (according to Predici) a lotof Cu(I) is generated at the beginning stage of the reaction and highmolecular weight polymers are obtained, since there is not enough Cu(II)in the system to deactivate growing chains.

(ii) Cu(I) is more soluble than Cu(II) with Me₆TREN ligand, thus duringthe transfer of active complex from preparation flask to the Schenkflask some of Cu(II) species which are not fully soluble in the transfermedium are lost. Therefore the real value of Cu species in the reactionmedium can be different, higher when Cu(I) is used.

All three experiments (WJ-03-60, 61 and 62) bimodal distribution ofmolecular weight was observed at the earliest stage of the reaction. Atlow conversion, 3%, a small fraction of high molecular weight polymerwas observed. This is probably a product of terminated chains which wereinitiated by radicals produced from the direct thermal decomposition ofAIBN which would indicate that the concentration of radicals at thebeginning stage of reaction can be high enough not only to quicklyreduce Cu(II) to Cu(I) but also initiate new polymer chains. Thefraction of terminated chains is small and disappears into the baselineof later GPC traces over time, due to overlapping with the intensesignal from main polymer product; FIG. 6.

The polymerization rates for all three reactions are the same andindependent of the amount of copper, Cu(I) or Cu(II) species, used atthe beginning of the reaction or the amount of ligand added. This provesthat the reaction is thermally controlled by thermal decomposition ofAIBN. In embodiments of the polymerization process a sequential orgradual addition of the initiator will overcome the initial excess ofradicals leading to lower level of uncontrolled polymerization.

Example 6 Synthesis of a PSt-b-PnBA Block Copolymer by ICAR and ARGETATRP

A PSt-Br macroinitiator (M_(w)=11000, M_(w)/M_(n)=1.12) (0.5 g, 4.5×10⁻²mmol), which was prepared by an embodiment of ICAR ATRP, was dissolvedin BA monomer (2.80 ml, 19.6 mmol) in a 10 mL Schlenk flask and bubbledwith nitrogen for 15 minutes. Next, a solution of CuCl₂ (0.13 mg,1.00×10⁻³ mmol)/Me₆TREN (1.32 μl, 5.00×10⁻³ mmol) complex indeoxygenated DMF (0.7 ml) was added. The resulting mixture was stirredfor 10 minutes before a purged solution of PhNHNH₂ (0.49 μl, 5.00×10⁻³mmol) in anisole (0.5 ml) was added. An initial sample was taken and thesealed flask was placed in a thermostated oil bath at 60° C. Sampleswere taken at timed intervals over 48.5 hours and analyzed by GC and GPC(M_(n, GPC)=65300, M_(w)/M_(n)=1.19, conversion=82%).

A clean shift in molecular weight indicates successful chain extensionof the PS-macroinitiator prepared by ICAR and formation of a blockcopolymer and thereby confirms the “livingness” of the macroinitiatorprepared by an embodiment of ICAR ATRP.

Example 7 Selection of Ligand

Several factors should be considered when attempting to optimize thereaction and select the appropriate conditions ICAR ATRP and AGET ATRPprocesses which are conducted with low concentrations of transitionmetal catalysts.

First, control over molecular weight distributions in ATRP is at leastin part dependent upon absolute deactivator concentration. The rateconstant of deactivation of a given catalyst can be calculated fromequation 4. In preferred embodiments of ICAR ATRP and AGET ATRP, thepolymerization process may comprise complexes with high values ofK_(ATRP) (resulting in sufficiently high concentrations of Cu^(II) insolution) and relatively fast deactivation rates. (i.e. above 10⁻⁸ oreven preferably above 10⁻⁷; [Tang, W., Tsarevsky, N. V. & Matyjaszewski,K.; J. Am. Chem. Soc. 128, 1598-1604.])

Second, in preferred embodiments of ICAR ATRP and AGET ATRP, thepolymerization process may comprise the catalyst that does notdissociate appreciably under the polymerization conditions. Thedissociation problem may be compounded by competitive complexationbetween the monomer and the ligand to the metal, as the monomer ispresent in very large excess compared to the catalyst in thesereactions.

Third, at very low concentrations of transition metal complex employedin ICAR ATRP, it was not immediately clear whether radicalconcentration, and consequently rate of polymerization, would begoverned by K_(ATRP) (as in normal ATRP) or by the rate of new radicalgeneration (as in RAFT).

In the initial runs listed in Table 10, four ATRP catalysts with a broadrange of K_(ATRP) values were selected to exemplify the scope ofembodiments of the ICAR ATRP process. These included the CuCl₂ complexesof tris[2-(dimethylamino)ethyl]amine (Me₆TREN),tris[(2-pyridyl)methyl]amine (TPMA),N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA), and4,4′-di-(5-nonyl)-2,2′-dipyridyl (dNbpy). ICAR ATRP of St was firstconducted at low temperature (60° C.) where organic radicals wereproduced solely by the slow decomposition of azobisisobutyronitrile(AIBN) (0.1 eq vs. ethyl 2-bromoisobutyrate (EtBrIB) initiator) in thepresence of 50 ppm of CuCl₂/L complexes (entries 1-4, Table 10).Interestingly, rates of polymerization differ by less than a factor oftwo among reactions catalyzed by CuCl₂/L complexes of Me₆TREN, TPMA,PMDETA, and dNbpy. This was initially surprising given that values ofK_(ATRP), which govern radical concentration and the rate ofpolymerization under normal and SR&NI ATRP conditions, for these fourcomplexes differ by more than four orders of magnitude in a “standard”ATRP.

TABLE 10 ICAR ATRP of Styrene Temp. Monomer/ [Cu] Ligand/ AIBN/ TimeConv. Entry (° C.) Initiator/Cu ppm Ratio to Cu Initiator (min) (%)M_(n, theo) M_(n, GPC) M_(w)/M_(n) 1 60 200 St/1/0.01 50 Me₆TREN/1 0.12760 44 8700 7900 1.12 2 60 200 St/1/0.01 50 TPMA/1 0.1 2880 39 78006800 1.09 3 60 200 St/1/0.01 50 PMDETA/1 0.1 2880 29 5600 4500 1.62 4 60200 St/1/0.01 50 dNbpy/2 0.1 2940 36 7200 5600 1.68 5 70 200 St/1/0.0150 Me₆TREN/1 0.1 2400 47 9500 7600 1.11 6 70 200 St/1/0.01 50 Me₆TREN/10.2 2500 60 11,900 10,000 1.15 7 70 200 St/1/0.01 50 Me₆TREN/1 0.4 114066 13,200 10,100 1.22 8 110 200 St/1/0.01 50 Me₆TREN/10 — 1775 65 12,90011,000 1.25 9 110 200 St/1/0.01 50 TPMA/10 — 1930 49 9800 9600 1.13 10110 200 St/1/0.002 10 TPMA/50 — 1720 42 8400 7600 1.38 11 110 200St/1/0.0002 1 TPMA/500 — 1700 55 11,000 8400 1.72 [St]₀/[EtBrIB]₀ = 200;[St]₀ = 5.82M; 50% anisole by volume.

While polymerizations mediated by CuCl₂/Me₆TREN and CuCl₂/TPMA were verywell controlled in terms of molecular weight and K_(T)/M_(n) (entries 1& 2, Table 10), control over M_(w)/M_(n) was significantly poorer in thepolymerization mediated by CuCl₂/PMDETA and CuCl₂/dNbpy (entries 3 & 4).This behavior is consistent with the fact that these two complexes havethe lowest of the four values of K_(ATRP).

An experiment conducted later with an even less active ATRP catalystcomplex, N-(n-octyl)-2-pyridylmethanimine, frequently used for the bulkpolymerization of more active methacrylate monomers, [Hovestad, N.J.;et.al.: Macromolecules 2000, 33, 4048-4052.] with a molar ratio ofreagents: St:I:Cu:L:AIBN=200:1:0.01:0.02:0.1 was even less controlled,especially at the beginning stage of reaction, resulting in even higherPDI (1.9) even though, as with PMDETA and dNbpy, absolute molecularweight control quite was good, (M_(n, theo) 8,000; M_(n, GPC) 6900.)

This would indicate that values for K_(ATRP) directly influencemolecular weight distribution and all reactions are controlled, sinceinitiation efficiency is high, and consequently terminal functionalityis present in the majority of polymer chains. The broader PDI is aconsequence of slower rate of deactivation. The polymers can be furtherchain extended and/or functionalized. The materials are not “dead” norwere they prepared in a totally uncontrolled reaction but remain“living” and will display different rheology and perhaps even differentphysical properties, particularly for block copolymers with segment(s)displaying broader PDI.

Such observations concerning attainable control can also be rationalizedbased on the stability of these complexes towards dissociation at highdilution and high temperature. The stability of Cu^(II) complexes ofPMDETA, Me₆TREN, and TPMA in aqueous media over a range of temperaturesare illustrated in FIG. 7 and can be used as a general guide for ligandselection in these systems. [Paoletti, P. & Ciampolini, M. (1967) Inorg.Chem. 6, 64; Anderegg, G., Hubmann, E., Podder, N. G. & Wenk, F. (1977)Helv. Chim. Acta 60, 123.] These stability constants suggest that such asignificant degree of dissociation of the CuCl and CuCl₂/PMDETAcomplexes would ultimately result in a lower absolute value ofdeactivator concentration, helping to explain the observed poor controlover M_(w)/M_(n) in this system (entry 3, Table 10). Converselypolymerizations mediated by CuCl₂/Me₆TREN and CuCl₂/TPMA were very wellcontrolled in terms of molecular weight distribution (M_(w)/M_(n)=1.1).The observed molecular weights were only slightly lower than theoreticalvalues. This lower than theoretical molecular weight is a likely resultof the constant generation of new chains throughout the polymerizationinherent in this ICAR ATRP process. Representative examples of theevolution of molecular weight with conversion and the linear first orderkinetics obtained in ICAR under these conditions are shown in FIG. 8.

The rates of polymerization differ by less than a factor of two amongreactions catalyzed by CuCl₂ complexes of Me₆TREN, TPMA, and PMDETA(entries 1-3, Table 10), suggesting K_(ATRP) may not play a significantrole in determining polymerization rate. However, control over molecularweight distribution was significantly lower in the polymerizationmediated by CuCl₂/PMDETA. This behavior can be rationalized based on thestability of these complexes towards dissociation at high dilution. Thefraction of non-dissociated Cu complex can be calculated from equation(5) knowing the stability constant (β^(j)) and total concentration ofthe complex ([Cu^(j)/L]₀, where j is the Cu oxidation state and L is theligand).

$\begin{matrix}{\frac{\lbrack {{Cu}^{j}/L} \rbrack}{\lbrack {{Cu}^{j}/L} \rbrack_{0}} = {1 - \frac{\sqrt{1 + {4{\beta^{j}\lbrack {{Cu}^{j}/L} \rbrack}_{0}}} - 1}{2{\beta^{j}\lbrack {{Cu}^{j}/L} \rbrack}_{0}}}} & (5)\end{matrix}$

According to the above dependence, for 90% of the catalyst to remain insolution at a total concentration of 10⁻⁶ M (the present lower limit forICAR or ARGET), the catalyst should have a stability constant largerthan 10⁸. This should be true for both the Cu^(I) and Cu^(II) states ofthe catalyst. From this perspective, ligands such as PMDETA displaying avalue of β^(j)<10⁸ at room temperature [Navon, N.; et al; Inorg. Chem.1999, 38, 3484] are not suitable for ICAR or ARGET ATRP if narrowmolecular weight distribution is desired. However this can be relaxed ifbroader molecular weight distribution is acceptable or even desired forcertain applications.

The stability constants for a large number of Cu complexes with variousN-based ligands are available in the literature. [Paoletti, P.;Ciampolini, M. Inorg. Chem. 1967, 6, 64: Anderegg, G.; Hubmann, E.;Podder, N. G.; Wenk, F. Helv. Chim. Acta 1977, 60, 123.] These valueshave been determined primarily in aqueous solutions at 25° C. but canstill be used as a general guide for ligand selection and all suitabletransition metal complexes formed with ligands displaying a β^(j)>10⁸ atroom temperature are herein incorporated as potentially suitablecomplexes for ICAR ATRP targeting narrow M_(w)/M_(n).

Furthermore, polymerizations in this study carried out at hightemperatures (60-110° C.) indicate destabilization of the ATRP catalystsat these temperatures and this should also be accounted for. Thethermochemistry of polyamine complexes of metal ions, including Cu^(II),has been extensively studied. [Paoletti, P.; Fabbrizzi, L.; Barbucci, R.Inorg. Chim. Acta Rev. 1973, 7, 43] The enthalpies of formation ofCu^(II) polyamine complexes are in the range of −10 to −20 kcal/mol, anda temperature increase from 25 to 110° C. should lead to a decrease inthe stability constant by 2-3 orders of magnitude. As discussed in thesereferences the temperature dependence of the stability of the Cu^(II)complexes of PMDETA, Me₆TREN, and TPMA is illustrated in FIG. 14 whichshows that the stability constant of Cu^(II)/PMDETA complexes isconsiderably lower than that of copper complexes formed with Me₆TREN orTPMA, which is consistent with the polymerization results in Table 10.Significant dissociation of the CuCl and CuCl₂/PMDETA complexes wouldultimately result in a lower absolute value of deactivator concentrationin the polymerization medium and consequently poorer control overM_(w)/M_(n).

Additionally, the coordination of various polar monomers such as St and(meth)acrylates to the Cu^(I)/PMDETA complex with non-coordinatinganions has recently been reported. [Braunecker, W. A.; et.al; J.Organometal. Chem. 2005, 690, 916; and Macromolecules 2005, 38, 4081.]While this complexation is comparatively weak the high concentration ofmonomer present in bulk, and even solution polymerization processesespecially at low ppm catalyst concentration, result in competitivecomplexation which could lead to a further destabilization of thecatalyst.

Additional experiments and kinetic simulations (vide infra) explore thepossibility that:

-   -   1) the rate of polymerization and radical concentration under        ICAR ATRP conditions are actually controlled by the rate of free        radical initiator decomposition and,    -   2) that the relative concentration of Cu^(I) and Cu^(II) present        in the reaction medium conform accordingly, as dictated by the        value for K_(ATRP).

Example 8 Varying Concentration of Free Radical Initiator and TransitionMetal

Among the controlled polymerizations conducted at 60° C., that mediatedby CuCl₂/Me₆TREN was (marginally) the fastest; however, it was stillrather slow, ˜50% conversion in 2 days. In experiments 5, 6 and 7 inTable 10 the temperature was increased to 70° C. and several reactionswere performed varying the amount of AIBN versus alkyl halide initiator.All three of these reactions mediated by CuCl₂/Me₆TREN were wellcontrolled. Increasing the amount of AIBN from 0.1 to 0.4 equivalentsresulted in just a slight increase in M_(w)/M_(n) (from 1.1 to 1.2),likely due to the higher number of terminated chains resulting from ahigher radical concentration produced in the early stages of thereaction. However, the rate of polymerization clearly increased withincreasing concentration of free radical initiator.

At higher temperatures (110° C.), where the complexes are more prone todissociate, a 10 fold excess of ligand compared to Cu was employed tohelp suppress dissociation. AIBN was not needed at this temperature forthe polymerization of styrene as the radical reducing agents, orcatalyst activators, were regenerated by thermal initiation of St. Inaccordance with the relative stabilities of the two complexes thepolymerization mediated by CuCl₂/TPMA was better controlled than thatmediated by CuCl₂/Me₆TREN (in terms of polydispersity) under theseconditions. Therefore, CuCl₂/TPMA was employed in an additional seriesof reactions to investigate the lower limits of catalyst concentrationnecessary for a controlled reaction. The Cu concentration was decreasedfrom 50 ppm to 10 and then to just 1 ppm (entries 10 and 11, Table 10).While a slight curvature was observed in the first order kinetics ofthese polymerizations (indicating the radical concentration is notconstant throughout the reactions) as expected from equation 3, thedecreased amount of Cu resulted in broader molecular weightdistributions (M_(w)/M_(n)˜1.4 and 1.7 for 10 and 1 ppm of Cu,respectively). FIG. 8 illustrates the control attainable with 1 ppm ofCu catalyst and compares the result to that obtained with 50 ppmcatalyst. When 1 ppm Cu was present molecular weights are slightlyhigher than theoretical values at very low conversion. However, quiteimpressively, just 1 ppm of Cu in the presence of excess TPMA wasultimately sufficient to control molecular weight and the terminalfunctionality in the ICAR ATRP of St although the molecular weightdistribution was broader.

Example 9 Polymerization of BA and MMA

ICAR ATRP of MMA was then attempted in the presence of AIBN and 50 ppmCu. The reaction was initiated by EtBPA in the presence of 0.01equivalents of CuCl₂/Me₆TREN at 60° C. The results are reported as inTable 11. Polymerization was not as well controlled as in analogousreactions of St (entry 1, Table 10). However, CuCl₂/TPMA proved veryefficient in mediating the controlled polymerization of MMA. Observedmolecular weights agreed well with theoretical values, linear firstorder kinetics are observed, and narrow molecular weight distributionswere attained (M_(w)/M_(n)˜1.2).

Both CuCl₂/Me₆TREN and CuCl₂/TPMA were employed in the polymerization ofBA initiated by EtBrIB. Acceptable polydispersities (M_(w)/M_(n)˜1.4)and good control over molecular weights were attained in bothpolymerizations (entries 3 & 4, Table 11). These experiments providedsufficient information to allow the system to be modeled.

TABLE 11 PBA prepared by ARGET ATRP under various conditions. Monomer/CuCl₂ Ligand/ RA/ Time Entry Initiator [ppm] Ratio to Cu Ratio to Cu(min) Conv. M_(n, theo) M_(n, GPC) M_(w)/M_(n)  1 200/1/0.01 50Me₆TREN/10 PhNHNH₂/10 1098 78 19,994 26,100 1.23  2 200/1/0.01 50Me₆TREN/3 PhNHNH₂/10 1098  33^(a) 8500 20,200 2.3  3 200/1/0.01 50TPMA/10 PhNHNH₂/10 3780 59 15,124 16,700 1.27  4 200/1/0.01 50 TPMA/3PhNHNH₂/10 1300  32^(a) 8202 8100 1.57  5 200/1/0.01 50 PMDETA/10PhNHNH₂/10 No Rxn  6 200/1/0.1 500 PMDETA/10 PhNHNH₂/10 1230 64 16,40525,481 1.70  7 156/1/0.007 50 Me₆TREN/10 — 1240 86 17,100 21,600 1.83  8156/1/0.007 50 Me₆TREN/10 NH₂NH₂/5 1950 90 17,800 20,520 1.20  9156/1/0.007 50 Me₆TREN/10 NH₂NH₂/10 1940 95 19,000 21,220 1.22 10156/1/0.007 50 Me₆TREN/10 NH₂NH₂/100 1200 96 19,100 19,970 1.26 11156/1/0.007 50 TPMA/10 NH₂NH₂/5 2520 41 8270 8690 1.32 12 156/1/0.007 50TPMA/10 NH₂NH₂/10 2520 60 11,840 12,490 1.25 13 156/1/0.007 50 TPMA/3NH₂NH₂/5 1200  28^(a) 5650 5540 1.37 14 156/1/0.007 50 TPMA/3 NH₂NH₂/101200  21^(a) 4320 4730 1.40 15^(b) 200/1/0.01 50 TPMA/3 MPO/10 No Rxn16^(b) 200/1/0.01 50 TPMA/3 MPO/200 1920  16^(a) 3200 4300 1.33 [BA]₀ =5.88M; 60° C., ~20% anisole by volume; M_(n, theo) = ([M]₀/[In]₀) ×conversion. ^(a)Polymerization did not occur past this limitedconversion. ^(b)90° C.

Example 10 Kinetic Modeling

The Predici program (version 6.3.1) was used for all kinetic modeling.It employs an adaptive Rothe method as a numerical strategy for timediscretization. The concentrations of all species can be followed withtime. Each actual calculation took 3-5 min to complete on a personalcomputer. The modeling was conducted in order to obtain a clear pictureof the kinetics of ICAR ATRP and determine whether the rate ofpolymerization in ICAR is governed by K_(ATRP) or by the rate of AIBNdecomposition. (AIBN is being used herein as an exemplary free radicalinitiator and it is believed that any free radical initiator can beused. One would just insert the appropriate rate of decomposition intothe formulae.) The multitude of parameters necessary for thesesimulations and typical rate constants for three CuBr₂/L complexes (withbipyridine (bpy), PMDETA, and TPMA) are shown in Table 12. These threecatalysts were chosen for the modeling studies since they represent abroad range of K_(ATRP) values. FIGS. 9-11 illustrate the results ofthese simulations for the ICAR polymerization of styrene. According tothese simulations, the polymerization rates for all three complexes areessentially the same (FIG. 9), and the first order kinetic plots are(nearly) linear. This suggests that the concentration of radicals remainalmost constant during the polymerization. The polymerization rate andradical concentration in ICAR ATRP does not appear to depend on thechoice of catalyst or value of K_(ATRP).

However, while the polymerization rate does not depend on the choice ofcatalyst, control over molecular weight and molecular weightdistribution are catalyst dependent. As shown in FIG. 10, when TPMA isused as the ligand (meaning a catalyst complex displaying appropriatevalues of activation and deactivation rate constants were employed inthe simulations), polydispersity is low throughout the reaction (<1.5)and approaches 1 at high conversion. Molecular weights increase linearlywith conversion and are approximately equal to theoretical values.Similar results are observed with PMDETA, although polydispersity isslightly higher than in the reaction with TPMA. However, polydispersityand molecular weights are less controlled when CuBr₂/(bpy)₂ is employedas the ligand to form the catalyst complex.

TABLE 12 Parameters and reaction conditions employed in Predicisimulations of ICAR ATRP of St Rate Value (M⁻¹ s⁻¹) Step constant TPMAPMDETA bpy I₂ → I + I k_(dc) 1.1E−5 (s⁻¹) X—Cu^(II) + I → Cu^(I) + IXk_(d2) 1E6   R—X + Cu^(I)

 R + X—Cu^(II) k_(act0) 15 0.65 0.03 K_(deact0) 1.9 × 10⁶ 1.1 × 10⁷ 8.3× 10⁶ R + R → R—R k_(t0) 2.5 × 10⁹ I + I → I—I I + R → I—R R + M → P(1)k_(i1) 1.35E4 I + M → IP(1) k_(i2) 4900     P(s) + M → P(s + 1) k_(p)340    IP(s) + M → IP(s + 1) PX(s) + Cu^(I) → P(s) + X—Cu^(II) k_(act)15 0.65 0.03 IPX(s) + Cu^(I) → IP(s) + X—Cu^(II) P(s) + X—Cu^(II) →PX(s) + Cu^(I) k_(deact) 1.9 × 10⁶ 1.1 × 10⁷ 8.3 × 10⁶ IP(s) + X—Cu^(II)→ IPX(s) + Cu^(I) P(s) + P(r) → D-ATRP(s + r) k_(tc)   1 × 10⁸ IP(s) +IP(r) → D-AIBN(s + r) P(s) + IP(r) → D-cross(s + r) P(s) + P(r) →D-ATRP(s) + DATRP(r) k_(td)   1 × 10⁷ IP(s) + IP(r) → D-AIBN(s) +DAIBN(r) P(s) + IP(r) → D-cross(s) + Dcross(r) DP = 200, 50 ppm of Cu,[St] = 5.82 M, 60° C.; I₂ = AIBN; RX = EtBrIB; M = St.St/EtBrIB/X—Cu^(II)/AIBN = 200/1/0.01/0.1; t_(50%) = 1.8E5 s Source ofthe values of rate constants (60° C.): k_(dc): the decomposition rateconstant for AIBN at 60° C. [Bamford, C. H. & Tipper, C. F. H. (1976)Comprehensive Chemical Kinetics, Vol. 14A: Free Radical Polymerization(American Elsevier, New York).] k_(d2): the deactivation rate constantfor free radical with X—Cu^(II) species, estimated from k_(deact) forATRP (10⁻⁵~10⁻⁸ M⁻¹ s⁻¹) [Matyjaszewski, K., Paik, H. -j., Zhou, P. &Diamanti, S. J. (2001) Macromolecules 34, 5125.] k_(act0), k_(act): theactivation rate constant for ATRP, measured at 35° C. and extrapolatedto 60° C. [Tang, W., Tsarevsky, N. V. & Matyjaszewski, K. (2006) J. Am.Chem. Soc. 128, 1598-1604.] k_(deact0), k_(deact): the deactivation rateconstant for ATRP, calculated from k_(act)/K_(ATRP) at 35° C. andextrapolated to 60° C. [Tang, W, Tsarevsky, N. V. & Matyjaszewski, K.(2006) J. Am. Chem. Soc. 128, 1598-1604.] k_(t0): the termination rateconstant for small molecular radicals. [Fischer, H, et. al. Acc. Chem.Res. (1987) 20, 200-206: and Angew. Chem., Int. Ed. (2001) 40,1340-1371. k_(i1) and k_(i2): the rate constant for addition of radicalsfrom EBIB (k_(i1)) and AIBN (k_(i2)) to styrene. Values are calculatedat 60° C. from the frequency factor and activation energy taken from theliterature [Fischer, H. & Radom, L. Angew. Chem., Int. Ed. (2001)40,1340-1371.1 k_(p): the addition and propagation rate constant. k_(p) istaken from the literature [Buback, M., et. al.: (1995) Macromol. Chem.Phys. 196, 3267-80.] k_(tc), k_(td): the termination rate constant forpolymeric radicals, the combination rate constant (k_(tc)) anddisproportion rate constant (k_(td)). Values estimated from theliterature [Buback, M., et. al.: (2002) Macromol. Chem. Phys. 203,2570-2582.]

To better illustrate all intricacies of the ICAR ATRP system, kineticplots were constructed, FIG. 11, where the rates of evolution andconcentrations of all species are illustrated on a double-logarithmicscale in the same figure (for CuBr₂/TPMA). It can be seen that thedormant species (the initial ATRP initiator, R—X, and the formedpolymeric dormant species) remain constant throughout the reaction,which gives rise to a linear increase in molecular weight with monomerconversion, and further indicates that most of the chain endfunctionality survives throughout the reaction. The ATRPquasi-equilibrium (R_(a)≈R_(da) throughout entire time span) was reachedalmost immediately (far before polymerization starts) due to the initialpresence of the Cu^(II) species. Once this state is reached, theconcentration of radicals, Cu^(I), and Cu^(II) remain essentiallyconstant, and the termination rate (R_(t)) approaches the decompositionrate of AIBN(R_(i)). The radical concentration can be estimated bysetting R_(i)=R_(t), i.e., 2k_(dc)[I₂]=2k_(t)[R]_(s) ².

$\begin{matrix}{\lbrack R\rbrack_{s} = {\sqrt{\frac{k_{dc}\lbrack I_{2} \rbrack}{k_{t}}} \approx \sqrt{\frac{{k_{dc}\lbrack I_{2} \rbrack}_{0}}{k_{t}}}}} & (7)\end{matrix}$

Equation (7) shows how the radical concentration (and hence, thepolymerization rate) under steady state conditions is primarilydependent on the AIBN decomposition rate constant, its concentration,and the radical termination rate constant. Radical concentration shouldtherefore not be governed by the choice of ATRP catalyst, K_(ATRP), orthe initial concentration of Cu^(II) species. This further suggests thatpolymerization rates can be adjusted with the choice of an appropriatefree radical initiator. These predictions are in relatively goodagreement with experimental observations, where apparent rates ofpolymerization in CuCl₂/Me₆TREN, TPMA and PMDETA mediatedpolymerizations (entries 1, 2, & 3, Table 10) are very similar.

While polymerization rates are controlled by the decomposition rate ofthe free radical initiator in ICAR ATRP (as they are in RAFT and freeradical polymerizations), control over polymer molecular weights andmolecular weight distribution are still governed by the ATRP equilibriumreactions. The ratio of polymerization rate to the deactivation rate,i.e., (k_(p)[M])/(k_(da)[Cu^(II)]), represents the number of monomerunits that will add to an actively propagating radical chain before itis deactivated to the dormant state. This provides a qualitative methodto estimate how well a given catalyst can control the molecular weightdistribution in a polymerization (as will be illustrated below). Sincesuch a small amount of Cu catalyst is employed in ICAR ATRP, catalystswith large values of K_(ATRP) (higher concentration of Cu^(II)) and fastdeactivation rate constants will minimize this ratio, allowing for moreuniform polymer chain growth, i.e. less monomer units added at eachactivation step, hence ultimately better control. Cu complexes with TPMAhave a large value of K_(ATRP) (˜7.9×10⁻⁶ at 60° C.). While the K_(ATRP)of Cu/PMDETA complex is much lower (˜5.9×10⁻⁸ at 60° C.), thedeactivation rate constant (k_(da)) for Cu/PMDETA is approximately sixtimes larger than that of TPMA, which compensates for the product ofk_(da)[Cu^(II)]. The Cu catalyst formed with bpy is the least activeamong the three complexes in this discussion, with K_(ATRP) (˜3.6×10⁻⁹)and a relatively small k_(da) (8.3×10⁶ M⁻¹ s⁻¹). The concentration ofCu^(II) species present at quasi-steady state can be estimated from theATRP equilibrium.

$\begin{matrix}{K_{ATRP} = {\frac{\lbrack {Cu}^{II} \rbrack \lbrack R\rbrack}{\lbrack {Cu}^{I} \rbrack \lbrack{RX}\rbrack} \approx \frac{\lbrack {Cu}^{II} \rbrack \lbrack R\rbrack}{{( {\lbrack {Cu}^{II} \rbrack_{0} - \lbrack {Cu}^{I} \rbrack} )\lbrack{RX}\rbrack}_{0}}}} & (8)\end{matrix}$

and where [R]_(s) is estimated from equation (7),

$\begin{matrix}{\lbrack {Cu}^{II} \rbrack = {\lbrack {Cu}^{II} \rbrack_{0}( {1 - \frac{1}{( {{K_{ATRP}\frac{\lbrack{RX}\rbrack_{0}}{\lbrack R\rbrack_{s}}} + 1} )}} )}} & (9)\end{matrix}$

As calculated from equation (9), and illustrated in FIG. 11, with theirrespective values of K_(ATRP), 90% of the total concentration of Cu inthe quasi-steady state exists in the Cu^(II) oxidation state forcomplexes with TPMA. This can be compared with just 7% for PMDETA and0.3% for bpy. The ratios of (k_(p)[M])/(k_(da)[Cu^(II)]) at thequasi-steady state can be calculated from equation (7) and (9) andindicate that approximately 4.0, 9.3, and 230 monomer units will add toa propagating chain every time it is activated by Cu/L complexes formedwith TPMA, PMDETA, and bpy, ligands respectively. These values arequalitatively consistent with the attainable control illustrated in FIG.11 for each system. The experimental value of M_(w)/M_(n) for the ICARpolymerization of St mediated by Cu complexed with TPMA is also in goodagreement with M_(w)/M_(n) shown in FIG. 6. However, in ICAR systemsemploying PMDETA as the ligand, control is overestimated in FIG. 6 ascomplex stability is not taken into account in these simulations.

Within this application the concept of Initiators for ContinuousActivator Regeneration in ATRP was introduced. ICAR ATRP allows use of50 ppm or less of Cu catalyst to mediate well-controlled polymerizationsof several radically (co)polymerizable monomers providing polymers withM_(w)/M_(n)<1.2 with this technique. Other monomers disclosed inincorporated references would also work.

The rational for selection of suitable Cu complexing ligands has beendiscussed in detail, primarily in regards to the value of K_(ATRP) for agiven catalyst but also with respect to complex stability at highdilution and at elevated temperatures. For these reasons, it wasdetermined that Me₆TREN and TPMA were more suitable ligands than PMDETAand dNbpy in ICAR ATRP at low Cu catalyst concentrations; however, otherligands meeting the criteria discussed herein would also be expected towork. Indeed this provides a model for examination of potential ligandsto predetermine whether they would be suitable for use in New ERA ATRPpreparation of materials meeting targeted applications.

Experimental data as well as simulations confirmed that the rate ofpolymerization in ICAR is governed by the rate of free radical initiatordecomposition (as in RAFT) while control is ultimately determined byK_(ATRP) and the rate of deactivation (as in ATRP).

Halogen Exchange

In further embodiments, ICAR ATRP and ARGET processes comprise a halogenexchange process. Halogen exchange processes comprise switching theradically transferable atom or group in a polymerization process toanother radically transferable atom or group. In an example of halogenexchange process, the catalyst employed for the second step of a blockpolymerization is chlorine based while that employed for the firstpolymerization step was bromine based. The halogen on the growing chainend was converted to a chlorine soon after the macroinitiator wasactivated thereby, in the case of bromine to chlorine, slowing down therate of propagation of the second polymerization to more closely tomatch the rate of initiation, for example. This cannot be accomplishedwhen the ratio of catalyst to end group on the macroinitiator issignificantly less than 1:1 and certainly not when less than 10%.

Two approaches were taken to resolve this issue.

One was a polymerization process comprising adding of a halogencontaining salt to interact with the transition metal catalyst complexand converting the radically transferable atom or group, such as thebromine counterion/ligand to a chlorine counterion/ligand, for example.Organic and inorganic salts with the desired halide counterion wereexamined and a preferred salt is lithium chloride.

Another approach was a copolymerization process for either ICAR ATRP orARGET ATRP comprising forming the second block with a different monomer,such as, for example, styrene which could be copolymerized with eitheracrylonitrile or a methacrylate and in the end group on the dormantgrowing polymer chain predominately comprised a styrene unit then themacromolecule could be controllably reactivated. This system was modeledby Predici and the results can be summarized as follows:

-   -   The k_(deact) (2E6) for MMA in the simulation is 10 times        smaller than before. This gives uncontrolled ICAR ATRP of MMA.        Also, the k_(art) for MMA is 2 times smaller. (FIG. 12)    -   Addition of styrene to the copolymerization process        significantly increase the level of control over polymerization        as seen in both DP and PDI. The addition of more styrene leads        to better results, which is reasonable since polymerization of        styrene is more controllable than MMA.    -   Kinetically, to have a better control, one would expect the        chain end to be preferentially capped with styrene as much as        possible. That is to say, more chains that are terminated P2X        (“2” refers to St) is preferable. While 5% of St is not enough        to provide control when 20% of styrene is added to the        copolymerization most of the chain ends (˜90%) becomes styrene        units. This is good enough for the control on DP but PDI is        fairly broad at 1.25. More St is needed if one wants to have        lower PDI. (FIG. 8)    -   The conclusion is that more styrene gives better control, and a        minimum 10% of St is needed to have a better control in such an        embodiment        An embodiment of ARGET ATRP process comprised adding        acrylonitrile to the polymerization of acrylate. The following        polymerization conditions were performed:        PBA-Br:Sty:AN:CuCl₂:Me₆TREN:Sn(EH)₂=1:2000:1300:0.1:1:1 in        anisole (1 vol equiv of monomers) at 80° C. Mn_(NMR) 250,000;        PDI 1.22.

Example 11 Expanding Range of Exemplified Reducing Agents

Several variables were examined in the ARGET ATRP processes comprisingbutyl acrylate (Table 11). In the first six experiments, the relativeconcentration of ligand to Cu is varied to trap evolving acid throughoutthe BA polymerization. The effect of the concentration of reducing agenton attainable control is investigated in the next eight experiments. Thefinal two experiments employ another reducing agent, 4-methoxyphenol(MPO), which is much less reducing than the hydrazine derivatives, tomediate ARGET reactions. Optimized conditions were then extended to theexcess reducing agent ATRP processes of MMA and St.

Mechanism of the Reduction Process and Relevance for Selected ReducingAgents.

Desmarquest studied the mechanism and kinetics of reduction of CuCl₂ byhydrazine. [Desmarquest, J. P.; Bloch, O. Electrochim. Acta 1968, 13,1109-1113]. The final product of oxidation of hydrazine is molecularnitrogen and each step of this multi-step process is accompanied byliberation of acid. The rate-determining step is the reversible transferof the first electron from N₂H₄ to the metal center leading to formationof the radical intermediate N₂H₃; it is characterized by rate constantsk₁=8×10⁻⁴ M⁻¹ s⁻¹ and k⁻¹=3×10³ M⁻¹ s⁻¹. The oxidation of PhNHNH₂ leadsto the formation of PhN═NH, again with the release of acid. [Kosower, E.M. Acc. Chem. Res. 1971, 4, 193-198.] However the studies of those redoxprocesses are complicated by the fact that both N₂H₄ and PhNHNH₂ formcomplexes with the Cu^(II) ions. [Srivastava, A. K.; Varshney, A. L.;Jain, P. C. J. Inorg. Nucl. Chem. 1980, 42, 47.] Competitivecomplexation with ligand will also have implications on the stability ofthe catalyst towards dissociation, and excess ligand may be required inARGET ATRP at concentrations where it is not required in ICAR ATRP.Retrospectively the role of trialkylamines in activating a catalystcomplex disclosed in incorporated patents based on application Ser. No.09/369,157 may be due to the reducing properties of the amine and wouldtherefore account for the faster reaction producing broader MWD.

The oxidation of MPO and its derivatives by CuCl₂ has also been studied.[Matsumoto, M.; Kobayashi, H. Synth. Commun. 1985, 15, 515.] The majorproduct is p-benzoquinone, but a small amount of o-chlorinated phenol isalso formed. Although the kinetics of the reduction process have notbeen studied in detail, it was demonstrated that reduction of CuCl₂ byMPO is relatively slow at ambient temperature.

Selection of the Ligand/Ligand Concentration.

The first six entries in Table 11 illustrate the dramatic difference inthe level of attainable control over molecular weight distribution ofpoly(butyl acrylate) depending on the ligand employed (PMDETA, Me₆TREN,or TPMA) and the concentration of the ligand relative to Cu. PDI,(M_(w)/M_(n)), for example, was much lower at similar conversions in areaction employing a 3 fold excess of TPMA to 50 ppm of CuCl₂ comparedto the analogous reaction with Me₆TREN (M_(w)/M_(n)=1.57 vs. 2.3,entries 2 & 4, Table 11). However, in both of these reactions, monomerconversion was limited to just 35%. No polymerization was observed afterthe first 24 hours in these reactions activated by a single addition ofphenylhydrazine. Similar results (in terms of conversion limited to<35%) were observed for analogous reactions with hydrazine and a 3 foldexcess of TPMA to Cu (entries 12 & 13, Table 11). When a larger excess,such as 10 fold, of free ligand was used, polymerization reached muchhigher conversions. In reactions mediated by 1:10 CuCl₂/Me₆TREN andCuCl₂/TPMA, molecular weight distributions were very well controlled(M_(w)/M_(n)=1.2-1.3, entries 1 & 3, Table 11). Observed molecularweights were also in good agreement with theoretical values,particularly in the case of TPMA.

However, no reaction was observed when a 10 fold excess of PMDETA to 50ppm Cu was employed. Even when 500 ppm Cu was used with PMDETA, controlover molecular weights and molecular weight distribution was worse(entries 5 & 6, Table 11). The behavior of the three complexes can inpart be rationalized based on their stability towards dissociation whichmay be further compounded by the fact that these reducing agents cancomplex with the catalyst. The observation that, 50 ppm of CuCl₂/PMDETAcan mediate an ICAR ATRP while it cannot mediate an ARGET ATRP can beattributed to the stability of the ligand towards protonation in thepresence of acid. Addition of a base should overcome this. Therefore,further embodiments of the polymerization process comprise adding a baseto the polymerization medium.

Stability was quantitatively determined by both the value of β^(j) andthe basicity of the ligand L. In the presence of an acid, the stabilityof the complex decreases by a factor of α_(L) (taking into account theamount of protonation or other side reactions of L) to a new value,termed the conditional stability constant β^(j,)*. If any of thereaction components (monomer, solvent, polymer, reducing agent or theproduct of its oxidation, designated by A) reacts with the copper ions,the stability of Cu^(j)/L decreases additionally by a factor of α_(Cu)^(j) taking into account these side reactions with A (characterized bystability constants β^(j) _(Cu) ^(j) _(Am)), according to eq (5).[Schwarzenbach, G. Die Komplexometrische Titration, 2nd ed.; Enke:Stuttgart, 1956. and Ringbom, A. Complexation in Analytical Chemistry;Interscience: New York, 1963.]

$\begin{matrix}{{\beta^{j,^{*}} = \frac{\beta^{j}}{\alpha_{L}\alpha_{{Cu}^{j}}}}{\alpha_{L} = {1 + \frac{\lbrack H^{+} \rbrack}{K_{a,r}} + \frac{\lbrack H^{+} \rbrack^{2}}{K_{a,r}K_{a,{r - 1}}} + \ldots + \frac{\lbrack H^{+} \rbrack^{r}}{K_{a,r}K_{a,{r - 1}}\ldots \; K_{a,1}}}}{\alpha_{{Cu}^{j}} = {1 + {\beta_{{Cu}^{j}A}^{j}\lbrack A\rbrack} + {\beta_{{Cu}^{j}A_{2}}^{j}\lbrack A\rbrack}^{2} + \ldots + {\beta_{{Cu}^{j}A_{m}}^{j}\lbrack A\rbrack}^{m}}}} & (5)\end{matrix}$

In the presence of side reaction, the amount of catalyst actuallypresent in the system can be calculated using equation (6) but with thenew conditional stability constant β^(j,)* instead of β^(j).

$\begin{matrix}{\frac{\lbrack {{Cu}^{j}/L} \rbrack}{\lbrack {{Cu}^{j}/L} \rbrack_{0}} = {1 - \frac{\sqrt{1 + {4{\beta^{j}\lbrack {{Cu}^{j}/L} \rbrack}_{0}}} - 1}{2{\beta^{j}\lbrack {{Cu}^{j}/L} \rbrack}_{0}}}} & (6)\end{matrix}$

FIG. 14 illustrates the pH dependence of the stability of the Cu^(II)complexes of PMDETA, Me₆TREN, and TPMA, calculated from equation 5(knowing the protonation constants which are available in literature)and shows that the complexes of basic ligands are very much destabilizedin acidic media, especially when their stability constants in theabsence of protonation (FIG. 7) are relatively low (e.g., the Cu^(II)complex of PMDETA). FIG. 7 also illustrates why PMDETA is lessapplicable for ARGET ATRP than the other ligands. Further the complex ofthe basic Me₆TREN is markedly more destabilized in acidic media thanthat of the less basic ligand TPMA. From the point of view oftemperature and pH stability, TPMA appears a preferred ligand for ARGETreactions where one of the byproducts of the reducing reaction is anacid.

Varying Concentrations of Reducing Agent and Cu.

The reducing agent will be quickly be consumed if too little is used,and too much might lead to fast and uncontrolled polymerizations orunwanted side reactions with the catalyst Amine based ligands can alsoact as reducing agents. [Wang, F.; Sayre, L. M. J. Am. Chem. Soc. 1992,114, 248-255.] The results of BA ARGET ATRP in the presence of variedamounts of N₂H₄ reducing agent are also presented Table 11. In a controlexperiment, a 10 fold excess of Me₆TREN (with four tertiary amine groupscapable of reducing Cu^(II)) was used in the absence of any otherreducing agent (entry 7, Table 11). Polymerization was initiated underthese conditions in the presence of alkyl halide, suggesting thatMe₆TREN can reduce Cu^(II) (M_(w)/M_(n)>1.8 at 86% conversion). Controlover M_(w)/M_(n) is much better in the presence of an added reducingagent, N₂H₄. First order linear kinetics are also observed when a 10fold excess of TPMA to Cu is used in the presence of a 5 fold excess ofN₂H₄ in a new ERA ATRP of BA. The rate of polymerization increases withincreasing concentration of N₂H₄, and first order kinetics remain linear(FIG. 15).

Rates of polymerization similarly increase with increasing concentrationof reducing agent when a 10 fold excess of Me₆TREN to Cu is employed.However, while good control is achieved over molecular weights andpolydispersity, linear first order kinetics are not observed in thepresence of a 5, 10, or 100 fold excess of N₂H₄ (entries 7, 8, & 9,Table 11, FIG. 16). While all five of these polymerizations are wellcontrolled in terms of narrow molecular weight distribution, steadilyincreasing molecular weights, and initiation efficiencies near 100%, thekinetics of the CuCl₂/Me₆TREN mediated system are not easily explained.These observations may be a function of the lower relative stability ofCu complexes with Me₆TREN vs. TPMA.

Examination of Other Reducing Agents.

In addition to hydrazines, another class of organic reducing agent wasinvestigated with MPO. When 10 equivalents of this reducing agent wereemployed with CuCl₂/TPMA in the ARGET ATRP of BA at 90° C., nopolymerization was observed. With the use of 200 equivalents of MPO, 16%conversion was reached in 32 hours (although PDI was relatively low,entries 15 & 16, Table 11). The inefficiency of MPO as a reducing agent(in terms of polymerization rate) compared to hydrazine andphenylhydrazine is fully consistent with the voltammetric data for theseorganic complexes; literature values for the oxidation waves of phenolsare typically one full volt more positive than the oxidation waves ofhydrazine derivatives in acetonitrile. [Sawyer, D. T.; Sobkowiak, A.;Roberts, J. J. L.; Eds. Electrochemistry for Chemists: Second Edition;Wiley: New York, 1995.]

Reducing agents such as glucose were also examined. The polymerizationprocess with glucose as the reducing agent stopped after 500 minutes orso. The kinetic plots and the molecular weight curves showed that eachtime ATRP stopped at 8-9 hours and then thermal initiated conventionalradical polymerization of styrene took place, see FIG. 17. Addition of abase can potentially extend the conversion of a polymerization withglucose as a reducing agent by diminishing the protonation of ligand andin fact triethylamine was effective (FIG. 17 a). In addition, increasingthe concentration of ligand also resulted in higher conversion. Anotherbase, 1,4-di-tert-butyl-pyridine was probably to weak to affectprotonation and the polymerization but the polymerization process stillstopped prior to high conversion (FIG. 17 b).

In these polymerizations the concentration of Cu^(II) was not at anextremely low level. In fact the stability constant of Me₆TREN and Cu isnot very high which makes the concentration of ligand very importantwhen [Cu] is low. When the concentration of ligand remained constant,the polymerization rate did not change too much with the change of[Cu^(II)]. An ARGET ATRP with styrene as monomer and glucose as reducingagent the concentration of Cu(II) can be reduced to 10 ppm or below andthe polymerization was observed to be under control; FIG. 18.

ARGET ATRP Processes Comprising Methyl Methacrylate (MMA) and Styrene.

ARGET ATRP processes comprising MMA initiated by EtBrIB at 60° C.resulted in observed molecular weights higher than theoretical valueswith M_(w)/M_(n)˜1.6 (entries 1 & 2, Table 12a). Better control wasobserved in the ARGET ATRP of MMA employing Sn(EH)₂ as a reducing agent.Polymerization of St was initiated by EtBriB at 90° C. (where thermalinitiation should not be significant) in the presence of a 10 foldexcess of PhNHNH₂ and ligand to 50 ppm of Cu. These reactions werefairly well controlled (M_(w)/M_(n)˜1.3, entries 3 & 4, Table 12a).However, polymerization reached limited conversions when phenylhydrazinewas employed as the reducing agent. This could be due to the instabilityof phenylhydrazine in the presence of air or UV light making itincompatible with strong oxidizing agents.

No styrene polymerization was observed in the presence of hydrazine. Toconfirm suspicions that the alkyl halide chain end was reacting withhydrazine and consuming the reducing agent in polymerizations ofstyrene, a model kinetic study was conducted with a low molecular weightanalogue of bromine-terminated polystyrene, namely 1-phenylethyl bromide(1-PhEtBr), with both N₂H₄ and PhNHNH₂. The nucleophilic substitutionwas followed by ¹H NMR in DMSO-d₆, where it was determined that thereaction with N₂H₄ was markedly faster than with the less basic PhNHNH₂.While nucleophilic substitution reactions will be slower in less polarsolvents (DMF/monomer) than in DMSO, these results provide asatisfactory explanation for the aforementioned observations. In thepresence of N₂H₄, the alkyl bromide oligomeric initiator reacts veryrapidly with the reducing agent and consumes it at an early stage of thereaction. As a result, essentially no polymerization is observed. WhenPhNHNH₂ is employed, the model reaction indicates the substitutionreaction is much slower, which is consistent with the observations thatpolymerization does occur but gradually slows down and stops beforemonomer conversion has been completed. While derivatives of hydrazineare obviously not well suited for polymerization of styrene earlierresults indicate that Sn(EH)₂ or glucose would be a more appropriatereducing agent in St ARGET ATRP indicating that one has to consider allside reactions when selecting the reducing agent. A series of MMApolymerizations were conducted with different initiators in order todetermine whether there would be a big difference in degree of controlover the polymerization. ARGET ATRP of MMA was controlled when veryactive initiators like BrPN was employed leading to polymers with lowPDI and molecular weights close to theoretical values. (Table 12b)

TABLE 12a PMMA and PS prepared by ARGET ATRP. Temp. CuCl₂ Ligand/ RA/Time Conv. Entry ° C. Monomer/Initiator/Cu [ppm] Ratio to Cu Ratio to Cu(min) (%) M_(n, theo) M_(n, GPC) M_(w)/M_(n) 1 60 200 MMA/1 EtBrIB/0.0150 Me₆TREN/10 NH₂NH₂/10 1200 20 4030 13,160 1.61 2 60 200 MMA/1EtBrIB/0.01 50 Me₆TREN/10 PhNHNH₂/10 1155 66 13,140 25,480 1.60 3 90 200St/1 EtBrIB/0.01 50 TPMA/10 PhNHNH₂/10 1620 5 1000 1100 1.40 4 90 200St/1 EtBrIB/0.01 50 Me₆TREN/10 PhNHNH₂/10 2820 37 7400 7100 1.27 5 90200 St/1 EtBrIB/0.01 50 TPMA/10 NH₂NH₂/10 NoRxn [St]₀ = 5.82M, 50% DMFby volume; [MMA]₀ = 6.23M; 50% DMF by volume; M_(n,theo) = ([M]₀/[In]₀)× conversion

TABLE 12b Experimental conditions and properties of PMMA prepared byARGET ATRP.^(a) Cu Time Conv. Label MMA In [ppm] CuCl₂ ligand Sn(EH)₂(min) (%) M_(n, theo) ^(b) M_(n, GPC) M_(w)/M_(n) WJ-05-02 200 1 50 0.010.06 0.1 300 0.82 16500 41500 1.35 PEBr TPMA WJ-05-04 200 1 50 0.01 0.060.1 300 0.78 16000 47800 1.31 PEBr TPMA WJ-04-86 200 1 50 0.01 0.06 0.1240 0.79 15800 55700 1.33 EtBP TPMA WJ-04-88 200 1 50 0.01 0.06 0.1 3600.86 17200 16600 1.18 BrPN TPMA ^(a)[MMA]₀/[In]₀ = 200; [MMA]₀ = 5.84M;T = 90° C., in anisole (0.5 volume equivalent vs. monomer);^(b)M_(n, theo) = ([M]₀/[In]₀) × conversion

ARGET ATRP Process Comprising MAO as a Reducing Reagent

In order to determine if the Cu^((II))/bpy complex could be reduced bymethyl aluminoxane (MAO) all three reagents were added sequentially to asealed flask, the reaction color changed from green to dark brownindicating MAO reduced Cu^((II)) (green) to Cu^((I)) (dark brown). TwoARGET ATRP processes were conducted comprising MAO as reducing agent.The results are shown below.

Reaction conditions^(a)) BA/EtBriB/Cu^((II))/TPMA/MAO Cu ppm Time (h)Conv. (%) Mn_(th) Mn_(GPC) Mw/Mn A) 200/1/1/2/1 5000 3 79 20,200 21,0001.32 B) 200/1/0.1/0.2/1 500 5 85 21,700 22,700 1.1 ^(a))BA; butylacrylate, EtBrIB; ethyl 2-bromoisobutyrate, temperature; 60° C., Anisolewas used as an internal standard (10 vol. % of BA)With the lower level of copper the reaction was better controlled andfollowed linear increase in conversion with time with final molecularweight close to theoretical values and showed quite narrow (PDI=1.10 in85% conversion). These results indicate that MAO is a good reducingreagent for ARGET ATRP and should work with reduced amounts of Cu andMAO.

Example 12 Synthesis of PSt-b-PBA Prepared by ICAR and ARGET ATRP

A polymerization process comprising a ratio of reagents[St]₀:[EtBrIB]₀:[CuCl₂]₀:[TPMA]₀=200:1:0.01:0.01; [St]₀=5.82 M; wasconducted at 60° C. in 50% anisole by volume providing a macroinitiatorof 11100 molecular weight and M_(w)/M_(n) 1.12. This macroinitiator wasthen extended with BA using ARGET ATRP, to minimize the production ofnew chains, employing[BA]₀:[PSt]₀:[CuCl₂]₀:[Me₆TREN]₀:[PhNHNH₂]₀=400:1:0.02:0.1:0.1;[BA]₀=5.88 M; and a reaction temperature of 60° C., in the presence of20% DMF by volume. Both polymerizations were carried out with 50 ppm ofcopper catalyst. Chain extension of the polystyrene macroinitiator withBA using ARGET ATRP with 50 ppm of copper proved very efficient and thefinal block copolymer had M_(n, GPC)=65300, M_(n, th)=52900,M_(w)/M_(n)=1.19. GPC traces of the polymers were monomodal after eachsynthetic step and illustrates the utility of these techniques in theproduction of block copolymers.

Example 13 (Co)Polymerization of Different Monomers and Exemplificationof Ability to Prepare High MW Polymers

ATRP processes with low concentration of copper catalyst, as low as orlower than 10 ppm, in the polymerization medium may suppress some of theside reactions associated with one or both oxidations states of thetransition metal complex and allow higher molecular weight copolymers tobe prepared. This example demonstrates this advantage of low catalystconcentrations.

Control Run: Copolymerization of Styrene and Acrylonitrile by ATRP(Amounts Entry 2 in Table 13a).

A Schlenk flask was charged with Me₆TREN ligand (7.2 μl, 0.031 mmol) andcopper (II) bromide (0.64 mg, 2.87 μmol), then anisole (5.52 ml) wasadded and the contents stirred. When the system became homogeneousstyrene (4.0 ml, 0.0349 mmol), acrylonitrile (1.52 ml, 0.0231 mmol) andethyl 2-bromoisobutyrate (8.12 μl, 0.0553 mmol) were added to the flask.After three freeze-pump-thaw cycles the flask was filled with nitrogen,then while the mixture was immersed in liquid nitrogen, 4.11 mg (0.0287mmol) of CuBr was added. The flask was sealed with a glass stopper,evacuated, and back-filled with nitrogen four times. After melting thereaction mixture and warming the contents of the flask to roomtemperature, the initial sample was taken and the sealed flask wasplaced in a thermostated oil bath at 80° C. Samples were taken at timedintervals and analyzed by gas chromatography (GC) and gel permeationchromatography (GPC) to follow the progress of the reaction. Thepolymerization was stopped by opening the flask and exposing thecatalyst to air. The overall polydispersity of the polymer for bothcatalytic systems was low, especially at the moderate stages of thecopolymerization, indicating good control over the reaction.

Considerations of ARGET ATRP of SAN: Copolymerization of Styrene andAcrylonitrile by ARGET ATRP (Amounts Appropriate for Entry 4 in Table13b)

Styrene (4.0 ml, 0.0349 mmol), acrylonitrile (1.52 ml, 0.0231 mmol) andanisole (4.22 ml) were added to a dry Schlenk flask. Then a solution ofCuCl₂ complex (0.223 mg, 1.66 μmol)/Me₆TREN (0.38 μl, 1.66 μmol) inanisole (0.8 ml) and the EBiB (8.12 μl, 0.0533 mmol) initiator wereadded. The resulting mixture was degassed by four freeze-pump-thawcycles. After melting the mixture, a purged solution of Sn(EH)₂ (8.95μl, 0.0278 mmol) and Me₆TREN (6.36 μl, 0.0278 mmol) in anisole (0.5 ml)was added. An initial sample was taken and the sealed flask was placedin thermostated oil bath at 80° C. Samples were taken at timed intervalsand analyzed by gas chromatography (GC) and gel permeationchromatography (GPC) to follow the progress of the reaction. Thepolymerization was stopped by opening the flask and exposing thecatalyst to air.

The azeotropic feed ratio of styrene and acrylonitrile was used for allexperiments. In order to examine some of the effects of catalystcomplexes on the reaction two catalytic systems were used for thesynthesis of SAN by ATRP; copper (I) bromide complexes with dNbpy andMe₆TREN respectively. Since Cu^(I) complexes with dNbpy areapproximately 10,000 times less active than Me₆TREN based coppercomplexes a significantly greater amount of dNbpy/Cu^(I) catalyst wasused in Table 13a entry 2 than the concentration of Me₆TREN basedcomplex used in entry 1 in order to provide a sufficiently fastpolymerization rate. Furthermore in the case of the reaction usingMe₆TREN as complexing agent 10% of deactivator was added to increaseinitiator efficiency due to the persistent radical effect.

A preferred ATRP catalyst possesses a low affinity for alkyl radicalsand hydrogen atoms on alkyl groups in order to suppress the contributionof side reactions in the transition metal mediated polymerization. Inthe case of copper-mediated ATRP of styrene loss of terminal halogenfunctionality by elimination of HX results in loss of chainfunctionality and consequently loss of control over the reaction.[Matyjaszewski, K.; Davis, K.; Patten, T. E.; Wei, M. Tetrahedron 1997,53, 15321-15329.] Studies with model compounds demonstrated that theelimination reaction was induced by the presence of the copper^(II)complex. This process was even more pronounced in bromine mediated ATRPthan in chlorine transfer systems and was more noticeable in thepresence of polar compounds. In the case of a SAN copolymerization thehighly polar nature of arylonitrile monomer exacerbates this specificside reaction. Another side reaction is due to a one electron oxidationof the polymeric radical by the copper^(II) catalyst to form acarbocation, which then eliminates a proton creating an unsaturated endgroup. This reaction can occur in hydrocarbon solvents. On the otherhand, Lazzari [Lazzari, M.; Chiantore, O.; Mendichi, R.; Lopez-Quintela,M. A. Macromolecular Chemistry and Physics 2005, 206, 1382-1388]proposed the reduction of the styryl radical by reaction with a protonsource forms anionic intermediates that can result in dead polymerchains. Furthermore, there are also side reactions associated with theacrylonitrile radical that have to be considered. According to previousstudies an acrylonitrile radical can easily react with copper^(I)complex to form a carboanion and copper^(II). The carboanion is a veryunstable and undergoes chain transfer termination. Additionally thecopper center can coordinated with either the monomer or polymer chainthrough the cyano group resulting in its deactivation or lowering itseffective concentration. Nevertheless on the base of copolymerizationparameters calculated by Baumann et al [Baumann, M.; Roland, A.-I.;Schmidt-Naake, G.; Fischer, H. Macromolecular Materials and Engineering2000, 280/281, 1-6] it is the styryl radical which is predominatelypresent in the active state (r_(s)=0.47±0.05, r_(AN)=0.03±0.03) and sidereactions typical for that radical are thought to be the main reason forchain deactivation. Probably all aforementioned reactions can occur tovarious degrees leading to less then ideal living behavior.

The experimental data for the copolymerizations are presented in Table13a and Table 13b and FIG. 19 presents the semilogarithmic kinetic plotfor polymerization of SAN with dNbpy and Me₆TREN/Cu^(I) catalysts. Itappears that neither dNbpy nor Me₆TREN provide a constant number ofgrowing radicals during the ATRP polymerization as severe deviationsfrom the straight line can be observed (FIG. 19). Monomer conversionstopped at around 50% and 60% respectively, showing the deactivation ofthe active species. However the overall polydispersity of the polymerfor both catalytic systems was low, especially at the moderate stages ofthe copolymerization, indicating good control over certain aspects ofthe reaction. The deactivation of active species for both catalyticsystems is clearly seen from the shape of SEC traces (FIG. 20). Theinitial narrow symmetrical peaks lose their regularity and a significantlow molecular weight shoulder becomes visible. The tail and irregularshape of the curves were sustained as the molecular weight increases.However it has to be pointed out, the overall level of control remainedsatisfactory.

TABLE 13a Experimental conditions and properties of SAN copolymersprepared by ATRP^(a) time conv M_(n) Entry Sty/AN EBiB CuBr CuBr₂ Ligand(h) (%) (×10⁻³⁾ M_(w)/M_(n) 1 600/390 1 0.5 0.05 0.055 117.6 56.0 48.11.18 (Me₆TREN) 2 600/390 1 4 — 8 117.6 46.9 47.1 1.20 (dNbpy) ^(a)Thereactions were conducted in anisole at 80° C. [Sty] = 3.17M.

TABLE 13b Experimental Conditions and Properties of SAN copolymersprepared by ARGET ATRP molar ratio Me₆TREN/ Cu Conc. of time convM_(n GPC) entry St/AN EBiB CuCl₂ Sn(EH)₂ (ppm) Sty (M) (h) (%) (×10⁻³⁾M_(w)/M_(n) 3 600/390 1 0.01 0.5/0.5 10 3.17 164 76.5 88.5 1.19 4600/390 1 0.03 0.5/0.5 30 3.17 67.0 80.6 70.9 1.18 5 600/390 1 0.050.5/0.5 50 3.17 21.7 71.1 99.3 1.22 6 1000/650  1 0.05 0.5/0.5 30 3.17116.0 58.0 78.1 1.23 7 2000/1300 1 0.165 1.0/1.0 50 3.17 91.3 48.5 126.11.23 8 2000/1300 1 0.10 1.0/1.0 30 3.17 69.4 41.7 100.3 1.23 9 2000/13001 0.10 1.0/1.0 30 5.07 46.4 69.6 211.8 1.42 10 2000/1300 1 0.03 0.5/0.510 5.07 92.2 60.0 166.2 1.26 11 600/390 0.5 (di-) 0.03 0.5/0.5 30 3.1718.7 77.5 157.0 1.28 12 600/390 0.33 (tri)    0.03 0.5/0.5 30 3.17 18.363.9 188.8 1.25 13 2000/1300 1 0.1 1.0/1.0 30 3.17 23.9 24.7 100.8 1.19

It appeared that it was not possible to suppress the side reactions byaccelerating the reaction rate through addition of an increased amountof Me₆TREN/Cu^(I). Indeed, the reaction rate was initially significantlyfaster, but at the same time the rate of irreversible termination ofgrowing radicals was also enhanced. The reaction stopped at lowconversion with very low initiation efficiency.

Synthesis of SAN by ATRP:

The main advantage of ARGET ATRP is that the system comprises continuousreactivation of a small amount of catalyst to maintain control. In mostsystems this means that catalyst solubility problems and purificationissues are easily overcome. ARGET ATRP of styrene and acrylonitrile wasconducted with ethyl 2-bromoisobutyrate (EBiB) as an initiator andMe₆TREN/Cu as the catalyst. Experimental conditions and properties ofthe SAN copolymers prepared by ARGET ATRP are shown in Table 13b. Inorder to optimize the amount of copper three different concentrations ofcatalyst were evaluated: 10, 30 and 50 ppm versus monomer (Table 13b,entries 3-5). The amount of the reducing agent, Sn(EH)₂ was keptconstant at 50 mol % of the initiator. Kinetic plots for allaforementioned reactions with different copper concentrations arepresented in FIG. 21. As expected the rate of polymerization increasedsignificantly as the copper concentration increased (FIG. 21). A slightdeviance from the straight line kinetic plots, FIG. 22, is visible whichmeans that the number of radicals present in the system changed, to someextent, during the reaction but control was maintained. The theoreticalmolecular weight of the copolymer samples did not vary significantlyfrom values obtained from GPC analysis. These results are significantlydifferent than the results from the normal ATRP when the same monomer toinitiator molar ratio was used. FIG. 23 shows a smooth shift of theentire molecular weight distribution toward higher molecular weight forthe system containing 30 ppm of catalyst: c.f. FIG. 21.

When a higher DP was targeted, (DP_(n)=1650), polymerization was slower.FIG. 24 presents the kinetic plots for the copolymerization of styreneand acrylonitrile with 30 ppm of copper versus monomer, as well as themolecular weight and polydispersities of the polymers formed in thissystem. Although the kinetic plot showed a very small deviation fromlinear characteristics and the molecular weight was only slightlydifferent from theoretical, a constant increase of molecular weightdistribution with conversion was observed. The increase inpolydispersity was visible on the SEC traces with tailing to the lowmolecular weight species which means formation of dead chains fromvarious termination reactions cannot be completely neglected and highmonomer conversion cannot be attained with good control overpolymerization under these conditions (FIG. 25).

Similar behavior was observed for the reaction where the targeted DP waseven higher, DP_(n)=3300. In this reaction a higher concentrations ofcopper catalyst (50 ppm versus monomer) and reducing agent were used dueto the very high dilution of initiator in the reaction media but an evenmore significant deviation from the straight line on the kinetic plotswas observed even though differences between theoretical molecularweight and that obtained from GPC measurements were negligible but againan increase in molecular weight distribution was observed when monomerconversion was still relatively low.

The amount of solvent was reduced in order to increase the rate ofmonomer conversion and retain control over the reaction, (Table 13b,entries 8-9). The actual concentration of monomers equaled 3.17 M and5.07 M respectively and 30 ppm catalyst was used in these examples.Significant differences in the reactions rate were observed when thekinetic plots of the reactions were compared. At higher monomerconcentration, 5.07 M, monomer conversion reached 70%, and while highmolecular weight polymer was obtained M_(n)=211,800 the molecular weightdistribution was broader than desired, M_(w)/M_(n)>1.4, but still withinthe range expected from a controlled reaction. Some deviance fromtheoretical molecular weight was also detected indicating somedeactivation of radicals through side reactions with catalyst.

When the amount of copper was decreased to 10 ppm, keeping monomerconcentration at the same level 5.07 M, the kinetic plot was linear,indicating a constant number of growing radicals, (Table 13b, entry 10).Deviation from theoretical molecular weight was also smaller andmolecular weight distribution was as low as 1.26 for SAN with molecularweight equals 166,200.

The high molecular weight SAN copolymer was obtained in a controlledradical polymerization, which leads to the conclusion that the very lowconcentration of catalyst used in this example significantly suppressesthe side reactions of growing radicals with copper species leading tothe preparation of well defined high molecular weight linear copolymers.

Copolymerization of SAN from a Macroinitiator:

A macroinitiator was also used for the copolymerization of styrene andacrylonitrile. The macroinitiator used was a poly(ethylene oxide) basedmacroinitiator containing a terminal 2-bromoisobutyrate group. Thereaction conditions are shown in Table 13b, entry 13. The linearcharacter of the kinetic plot indicates a constant number of growingspecies in the reaction medium, up to 20% of monomer conversion afterwhich the rate of monomer consumption was reduced. Slight discrepanciesbetween theoretical molecular weight and that determined by GPC wasobserved only the early stage of the polymerization, due to the presenceof the macroinitiator, and the molecular weight distribution remainedlow at each stage of the polymerization pointing to the high degree ofcontrol over the process.

Synthesis of SAN from Di- and Trifunctional Initiators:

The reaction conditions developed using a monofunctional initiator(EtBriBu) and PEO-macroinitiator were employed in a series of reactionswith multifunctional initiators. Identical concentrations of catalystand initiator were used in each system which should provide the samenumber of growing radicals. The rate of polymerization was the same withall the initiators, indicating that each initiating site wasindependently participating in the polymerizations. However when theconcentration of active species was kept constant for initiators withdifferent functionality, the monomer-to-initiator ratio changes for eachsystem which results in, different rates of change of absolute molecularweight during polymerizations. Noticeable deviations from theoreticalvalues were observed only at higher molecular weight in case of SANsynthesized from di- and trifunctional initiating species. However thepolydispersity of the polymer remained low M_(w)/M_(n)<1.3, throughoutthe reactions indicating good control during each stage of the reaction.Using triple detector SEC, the absolute molecular weights of (branched)PSAN and PEO block polymers were measured. The value dn/dc of thepolymer was determined using a known concentration of linear PSANsolution in THF. The value of dn/dc for a copolymer of SAN with certaincomposition (styrene=60%) is known and is equal to 0.157. The blockpolymer of PEO₅₀₀₀-b-PSAN contains less than 5 wt % of PEO moiety sothat the results obtained from 3D-SEC were still reliable. In addition,the number-average intrinsic viscosity was also given by the instrument.Table 12 compares the data measured by normal GPC and 3D-SEC.

TABLE 12 Relative and absolute molecular weight data for SAN copolymersprepared from mono-, di-, and trifunctional initiators as well as PEObased macroinitiator M_(n) initiator SEC^(a) 3D-SEC^(b) [η]_(n) ^(c)(dL/g) EBiB 100 100 116 900 0.633 EBiB 211 000 216 600 1.013 di-BriBu 98 100  92 100 0.569 di-BriBu 157 000 160 400 0.846 tri-BriBu  98 400126 000 0.602 tri-BriBu 188 800 203 700 0.790 PEO₅₀₀₀-BriBu 100 800  98900 0.641 ^(a)Measured by SEC with linear polystyrene standard.^(b)Measured by triple detection SEC and the dn/dc value of SANcopolymer (60% styrene) is determined as 0.157 mL/g. ^(c)Number-averageintrinsic viscosity determined by 3D-SEC.

There was no significant difference between standard GPC and 3D-SEC forany of the copolymers, meaning the results obtained from standard GPCare reliable. Changes of the number-average intrinsic viscosity measuredusing the on-line viscometer corresponds to the expected trend forlinear and star polymers: a star polymer has a lower viscosity thanlinear one with a similar molecular weight.

ARGET ATRP allows a significant reduction in the amount of catalystcomplex employed in the reaction and it was possible to synthesize highmolecular weight polymer due to significant suppression of sidereactions through reduction of the absolute concentration of the copperspecies in the system. Side reactions between the growing radicals andthe catalyst were avoided to a significant extent. The amount of copperspecies present in the system can be as low as 10 ppm without loss ofcontrol making this process very useful for industrial scale production.Polymerization with mono-, di- and trifunctional initiators lowmolecular weight initiators and a macroinitiator resulted in theformation of well-defined polymers with controlled architecture.

Synthesis of SiO₂—PSAN:

SiO₂—Br (20 nm):Sty/AN/SiO₂—Br/CuCl₂/Me₆TREN/Sn(EH)₂=2000:1300:1:0.10:1.0:1.0 in anisole(1 vol equiv of monomer) at 80° C. Cu: 30 ppm. The SEC trace of thesample taken at 42.4 h was symmetric with low polydispersity, indicatingthat there was no coupling reaction during the polymerization. From ourprevious experience, the initiator efficiency for polymerization of SANon small silica particles is around 30%. The conversion at 42.4 h wasestimated about 14% providing tethered chains with a molecular weight of127,000 and PDI of 1.3 (measured from cleaved polymer). However as iscommon with multifunctional initiators in solution polymerization whenthe reaction was driven to higher conversion the polydispersityincreased and some insoluble gel was observed, indicating somecrosslinking had occurred. Composite structures can be prepared by ARGETATRP processes.

As disclosed in other patent applications the use of miniemulsion ATRPallows for compartmentalization of multifunctional initiators in thewell dispersed droplets and reduces crosslinking as a consequence of lowinstantaneous concentration of radicals in a given droplet.

HEMA-TMS by ARGET ATRP:

Several polymerizations of HEMA-TMS were conducted targeting a highmolecular weight polymer suitable as a backbone for a grafting frompolymerization. In the past when targeting very high molecular weightp(HEMA-TMS) RAFT was selected as the appropriate CRP. In this series ofruns the ratio of monomer to initiator was 10,000 to 1 and the amount ofcatalyst, tin and solvent were varied to find the best conditions. Thebest conditions wereHEMA-TMS:EBiB:CuCl₂:Me₆TREN:Sn(EH)₂=10,000:1:2:25:25. in 50% anisole at50° C. The final polymer had M_(n)=2.45×10⁶ and M_(w)=5.27×10⁶ with aPDI of 1.63.

It is probable that early in the reaction there was some initialinitiator/initiator termination reactions resulting a higher actualmolecular weight than targeted for the selected level of conversion. Asdisclosed below, this phenomenon can be avoided by a sequential additionof the reducing agent which allows a slower activation/initiationprocedure followed by an increased rate of polymerization.

High Molecular Weight Polyacrylonitrile (PAN) by ATRP

PAN is not soluble in monomer and most organic solvents such as THF,anisole, methanol, acetone. Generally when targeting high Mn one alsoattains high PDI and there is a non-linear first order kinetic plot ofmonomer consumption (ln(M₀/M) vs. t) and inadequate characterization ofMn by GPC (DMF). The broader PDI can be attributed to side reactions.

-   -   Side reaction 2: too fast activation (˜10 times faster than        standard ATRP Initiator EBiB)→too much termination.    -   Side reaction 2: reduction of the radical to an anion by        copper^(I): R*+Cu^(II)→R⁻ resulting in loss of chain end.    -   Side reaction 3: Cu center coordinating to cyano groups on        monomers or polymers resulting in loss of catalyst:        P—Br+R—CN→P—CN—R

The following variables were examined and the best reagents arehighlighted in bold font.

Solvent: DMF, EC, DMSO

Initiator: BPN, CPN, BAN, CAN

Reducing agent: Sn(EH)₂, ascorbic acid, glucose, phenylhydrazine

Temperature: 65, 55, 40, 25° C.

Amount of Cu^(II)Cl₂: 100, 75, 50, 25, 10 ppm

Initially the ARGET polymerization of acrylonitrile was slow thereforethe reaction was examined with the addition of ascorbic acid and athigher temperature. Addition of ascorbic acid led to a fast reactionwhile higher temperature had no significant advantage. The use ofSn(EH)₂ at 55° C. resulted in the production of a polymer with anacceptable PDI. The broader PDI was caused by the presence of a longtail in the GPC curve which was attributed to fast increase of initialmolecular weight. The initiation was slowed down by using ClPN withSn(EH)₂ and later ClPN/BrAN with glucose at 25 ppm Cu but this resultedin a slower reaction with worse control!

A series of experiments were run with glucose as reducing agent. Thebest results were obtained at 40-65° C. in DMSO as solvent. The moleratio reagents used in such a reaction were:

AN:BrPN:CuCl₂:TPMA:glucose=4000:1:0.2:2.2:2 in DMSO (2.5 vol equiv ofmonomer) at 40° C. This is the equivalent of 50 ppm Cu in the reaction.It is noteworthy that both the reaction medium and product werecolorless. Conversion was estimated by NMR to be ˜69% after 166 hoursreaction. GPC indicates that measured Mn/3 is close to theoreticalmolecular weight based on conversion data. The clean shift of the GPCtraces for this run can be seen in FIG. 18. This example indicates thatthe reducing agent should be matched with the ligand and monomer(s). TheMn/3 of the sample was 135,000 and the polymer had a PDI of 1.18indicating that there was almost no termination during thepolymerization because when the reaction temperature is decreased, thechain transfer reaction rate is also decreased to a significant degree.

PBA-b-PSAN by ARGET ATRP

PBA-Br:Sty:AN:CuCl₂:Me₆TREN:Sn(EH)₂=1:2000:1300:0.1:1:1 in anisole (1vol equiv of monomers) at 80° C. Mn 250,000 PDI 1.22.

Example 14 Polymerization of Monomers Bearing Additional FunctionalGroups Preparation of AMPSA₂₇BA₄₆₈AMPSA₂₇ by AGET ATRP:

AMPSA based block copolymers are desired as templating agents for thepreparation of flexible conductive polymers however their preparation bystandard ATRP techniques have met with a limitation on the MW of theAMPSA block. The following example was run under conditions developedfor the preparation of AMPSA₂₇BA₄₆₈AMPSA₂₇ in a standard ATRP reaction.The conditions for this AGET ATRP are similar to those used in the‘regular’ ATRP polymerization of AMPSA, with the addition of aproportion of ascorbic acid in addition to the other components. In thistype of reaction the role of the added reducing agent is to reactivateany excess Cu^(II) formed by termination reactions.

General Procedure:

AMPSA (16.6 g) was added to a Schlenk flask, along with 8.2 g of PBAmacroinitiator (MW 60,000 g/mol) and degassed for 30 minutes. Degassedtributylamine (19.2 mL) and degassed DMF (48 mL) were then added,followed by stirring until the AMPSA and PBA dissolved, then another 20minutes of degassing. Copper chloride (79.2 mg), ascorbic acid (47 mg)and bpy (87.6 mg) were added to a separate Schlenk flask, and oxygen wasremoved by 3 cycles of vacuum pumping and nitrogen purging. Degassed DMF(3 mL) was then added to this mixture, and it was stirred for 10 minutesto allow the copper complex to form. A portion of the copper complexsolution (1 mL) was then added to the reaction flask, followed bydegassing for several minutes. The flask was lowered into a 60° C. oilbath, and the reaction was allowed to run overnight. The reaction wasquenched by addition of DMF and exposure to air. The DMF/polymersolution was poured slowly into water, and the resultant micellarsolution was purified by dialysis for two days. According to DMF GPCanalysis of the resultant product, the difunctional macroinitiator waschain extended with polyAMPSA. After passing the polymer through a Dowexion exchange column, the molecular weight decreased (elution volumeincreased) due to loss of the tributylammonium counter-ion. Themolecular weight of the macroinitiator was 60,000 g/mol by DMF GPC,while the final acid-containing block copolymer had a molecular weightof 82,000 g/mol, with a PDI of 1.13. According to elemental analysisthis polymer is 27 wt % AMPSA, with a DP of AMPSA₅₃BA₄₆₈AMPSA₅₃ i.e.slightly less than twice the amount of AMPSA present in polymersprepared by conventional ATRP.

Again this novel activation procedure reduces side reactions andprovides materials with higher AMPSA content suitable for use inpreparing templated conducting polymers with good mechanical properties.

AGET ATRP of NIPAAm:

TPMA has been found to be an effective ligand for AGET ATRP of NIPAAm inwater when using a solvent such as 2-propanol. The polymerization can bedriven to >90% conversion and low polydispersity polymers can beobtained. When a ratio of NIPAAm (200), methylchloropropionate (1), TPMA(1), CuCl₂ (1), ascorbic acid (0.5) in 2-propoanol, 91% conversion wasreached with Mn=20,000 and PDI=1.16. In an attempt to obtain highermolecular weight polymer the molar ratio of NIPAAm to the other reagentswas increased to 500. 1.0 grams of NIPAAm was used with 1.7 mL of2-propoanol and 0.3 mL of water to help dissolve the ascorbic acid. TheNIPAAm, CuCl₂, and TPMA were vacuum dried for 20 minutes. 1.2 mL of2-propanol and MCP were added. This was bubbled with nitrogen for 40minutes. In a separate flask, ascorbic acid was dried under vacuum andmixed with 0.5 mL, 2-propanol and 0.3 mL of water and bubbled withnitrogen for 40 minutes. The flasks were combined to start the reaction.A molecular weight of 42,000 was obtained after 5 hours and the polymerdisplayed a PDI of 1.10.

AGET ATRP of OEOMA 475 in Water, Targeting DP=1000:

The AGET ATRP of OEOMA 475 using a bromine functionalized PEO5000initiator was investigated targeting high molecular weight polymer, i.e.DP=1000. In the first set of experiments, the amount of reducing agent(ascorbic acid) was varied from 10 to 30 mol % of CuBr₂. The results aresummarized in the following table entries 1-3. Increasing the amount ofascorbic acid led to higher conversion. When ascorbic acid was added atonly 10 mol % or 15 mol % of Cu^(II) the reaction reached limitedconversion as evidenced by the plateau on the first order kinetic plots.Molecular weight linearly increased with conversion, and narrowpolydispersity and monomodal distribution were observed. However, with30% of ascorbic acid, although higher conversion was achieved,polydispersity was broader and a shoulder was observed on GPC traces.

TABLE 15a AGET ATRP of OEOMA 475 in water at 30° C. [CuBr₂] [Asc.Ac.]time conversion M_(n,th) M_(n,exp) Exp. (mM) (mM) [AscAc]₀/[CuBr₂]₀ (%)min. (%) (g/mol) (g/mol) PDI 1 0.32 0.032 10 30 38 186000 135000 1.24 20.32 0.048 15 60 47 228400 170000 1.24 3 0.32 0.096 30 90 86 414000364000 1.86 Reaction conditions: [OEOMA 475]/[PEO5000-Br]/[CuBr₂]/[TPMA]= 1000/1/0.5/0.5. Water/monomer ratio (v/v) = 2.5 for all experiments.

In a second set of experiments, the water to monomer ratio (v/v) wasdecreased thereby increasing the concentration of catalyst in themedium. The molar ratio of ascorbic acid to CuBr₂ was chosen as 15%,since this condition seemed to provide a good balance between rate ofpolymerization and control among the previous experiments. Results aresummarized as entries 4-6 in the table below. Decreasing the water tomonomer ratio (v/v) led to higher conversion. First order kinetic plotswere linear but a plateau was still observed. Molecular weight linearlyincreased with conversion, monomodal distributions were observed andpolydispersities remained quite low even at high conversion.

TABLE 15b AGET ATRP of OEOMA 475 in water at 30° C. [CuBr₂] [Asc. Ac.]Water/Monomer time conversion M_(n,th) M_(n,exp) Exp. (mM) (mM) (v/v)(min.) (%) (g/mol) (g/mol) PDI 4 0.444 0.067 1.5 60 66 319000 196000 1.35 0.368 0.0553 2 60 70 338000 223000 1.37 6 0.32 0.048 2.5 60 47 228400170000 1.24 Reaction conditions: [OEOMA 475]/[PEO5000-Br]/[CuBr₂]/[TPMA]= 1000/1/0.5/0.5. [Asc Ac]₀/[CuBr₂]₀ = 15% for all experiments.

In a third set of experiments, sequential addition of the reducing agentwas performed. Ascorbic acid was added at zero time and at regular timeintervals during the polymerization. Results are summarized in the Table15c, entries 7-9. Since the reaction reached limited conversion after 30minutes when ascorbic acid was added at 15 mol % of CuBr₂ to start thepolymerization, the same quantity was added every 30 minutes. Asexpected, the first order kinetic plot was linear and 76% conversion wasachieved within 2 hours. Molecular weight increased linearly withconversion, and monomodal molecular weight distribution was observed andwhile polydispersity increased to 1.49 the GPC curve was still quitenarrow and symmetrical.

When the water to monomer ratio was decreased from 2.5 to 2.0 by volume,keeping the same conditions, the first order kinetic plot was stilllinear but bimodality was observed in the GPC traces.

TABLE 15c AGET ATRP of OEOMA 475 in water at 30° C. [CuBr₂] [Asc.Ac.][AscAc]₀/[CuBr₂]₀ time conversion M_(n,th) M_(n,exp) Exp. (mM) (mM) (%)(min.) (%) (g/mol) (g/mol) PDI 7 0.32 0.048 15 60 47 228400 170000 1.248 0.32 0.048 4 × 15 120 76 367000 280000 1.49 9 0.368 0.0553 3 × 15 9075 361000 230000 1.47 Reaction conditions: [OEOMA475]/[PEO5000-Br]/[CuBr₂]/[TPMA]/[Asc Ac]₀ = 1000/1/0.5/0.5/0.075.Sequential or gradual addition of the reducing agent therefore doesallow one to control the rate of reduction and hence the ratio of Cu^(I)to Cu^(II) throughout the reaction and attain higher molecular weightmaterials.

Example 15 Development of a Simple Procedure for “Grafting from” FlatSurfaces

The main goal of this example is to define and demonstrate a very simpleprocedure for grafting from flat surfaces with different monomers. Theinitial target was to perform AGET or ARGET ATRP at room temperature inthe presence of a limited amount of air in a dish (e.g. Petri dish)which can be just simply covered and insulated with parafilm. In thefirst experiment a Petri dish was used, covered and insulated withparafilm. The polymerization did not occur even after degassing all thereagents with N₂ and adding a higher amount of reducing agent Sn(EH)₂.

The next set of experiments were performed in a weighing dish, which isequipped with ground cover and is deeper than a Petri dish. This type offlask allows ready access to the contents but can be filled close to thetop with liquids then sealed in a similar manner to a commercialreactor. The conditions for the reaction, run WJ-04-71, and results areshown below.

Conditions for the Reaction

Reducing T Sample Monomer Initiator Cu^(II) Ligand agent [° C.] WJ-04-nBA EtBrIB CuCl₂ Me₆TREN Sn(EH)₂ r.t. 71 (DP = 600) (1 eq.) (1 eq.) (1eq.) (0.5 eq.) Solvent: anisole/acetone 0.05/0.05 volume equivalents vs.M. 1.5 equivalents of Sn(EH)₂ was added after 49.5 h.

All the reagents were mixed together in a weighing dish and bubbled withN₂ for 20 min Next, the initial sample was taken and then the reducingagent was added and reactor was sealed. After 49.5 h reactor was openedand a test sample was taken. (Time zero sample in Table 16) To check ifpolymerization can be continued the reaction mixture was bubbled with N₂again and an extra amount of Sn(EH)₂ was added. Reaction was stoppedafter 95 h and the molecular weight of the tethered polymer hadincreased while PDI remained low thereby showing that two sequentialcontrolled ARGET ATRP polymerizations had been conducted.

TABLE 16 Results Name of Mw Mw Conv. sample time (GPC) theor. nBA PDIWJ-04-71 0 0 0 0 0 2910 6400 9400 0.12 1.31 5700 8700 12300 0.16 1.28← + Sn(EH)₂

Each opening of the reactor in Example 15 resulted in addition of air,which can consume catalyst and reducing agent, however, the molecularweight of the polymer moved to higher molecular weight without any signof tailing. The polymerizations were well controlled, molecular weightswere close to theoretical values and low PDI (1.28) was observed. Thisexample does show that an ATRP can be conducted from a solid flatsurface and that the initial presence of a small amount of air can becompensated for by addition of excess reducing agent.

Further the successive reactivation of the tethered chains shows thattethered block copolymers can be prepared by this procedure and/or theterminal functionality can be modified to attaché additional responsivefunctionality.

Example 16 Non-Acid Forming Reduction Reactions

A consequence of the examination of a broader spectrum of reducingagents suggests that it would be advantageous in certain circumstancesto conduct the reduction with an agent that does not release an acidupon oxidation. Examples of such reducing agents are viologens andsulfites. The reducing properties of viologens, which undergo electrontransfer rather than hydrogen transfer seen with of ascorbic acid,2,3-dimethoxy-5-methyl-1,4-hydroquinone, and the vitamin E analogTrolox, are easily adjusted by changing the substituents on themolecule. This would modify Scheme 1 in that the X atom or group nolonger results in the formation of an acid which should reduce the sidereactions associated with acid forming reducing agents and allow thereaction to be conducted in the absence of excess ligand as demonstratedin ICAR ATRP.

1. A polymerization process, comprising: polymerizing one or moreradically (co)polymerizable monomers in the presence of: at least onetransition metal catalyst complex; an ATRP initiator; and a reducingagent, wherein the transition metal catalyst complex is present at lessthan 10⁻³ mole compared to the moles of radically transferable atoms orgroups present on the ATRP initiator.
 2. The polymerization process ofclaim 1, wherein the reducing agent comprises one or more compoundscapable of reducing the transition metal catalyst by one oxidationstate.
 3. The polymerization process of claim 2, wherein thepolymerization process is one of a suspension polymerization process, anemulsion polymerization process, a miniemulsion polymerization process,or a microemulsion polymerization process.
 4. The polymerization processof claim 2, wherein the reducing agent is selected from the groupconsisting of includes SO₂, sulfites, bisulfites, thiosulfites,mercaptans, hydroxylamines, amines, hydrazine (N₂H₄), phenylhydrazine(PhNHNH₂), hydrazones, hydroquinone, food preservatives, flavonoids,beta carotene, vitamin A, α-tocopherols, vitamin E, propyl gallate,octyl gallate, butylated hydroxyanisole (BHA), butylated hydroxytoluene(BHT), propionic acids, ascorbic acid, sorbates, reducing sugars, sugarscomprising an aldehyde group, glucose, lactose, fructose, dextrose,potassium tartrate, nitrites, nitrites, dextrin, aldehydes, glycine, andtransition metal salts.
 5. The polymerization process of claim 1,wherein the polymerizing is conducted in a polymerization medium and theconcentration of transition metal in the reaction is less than 100 ppm.6. The polymerization process of claim 5, wherein the concentration oftransition metal in the reaction is less than 50 ppm.
 7. Thepolymerization process of claim 5, wherein the concentration oftransition metal in the reaction is less than 10 ppm.
 8. Thepolymerization process of claim 1, wherein the transition metal catalystcomplex is a (pseudo)halogen transfer agent.
 9. The polymerizationprocess of claim 1, wherein the transition metal catalyst complex in anactivator state is generated in situ from the reduction of thetransition metal catalyst complex in the deactivator state by thereducing agent.
 10. The polymerization process of claim 1, wherein thetransition metal catalyst complex comprises a transition metal and aligand.
 11. The polymerization process of claim 10, wherein the ligandand transition metal form a transition metal catalyst complex whereinthe higher oxidation state is an efficient deactivator.
 12. Thepolymerization process of claim 10, wherein conditional stabilityconstant of the transition metal catalyst complex is greater than 10⁶.13. The polymerization process of claim 10, wherein the ligand on thetransition metal catalyst complex and the reducing agent are selected tocontrol the PDI of the formed polymer.
 14. The polymerization process ofclaim 10, wherein the ligand is selected to provide a stable complex inthe presence of an acid.
 15. The polymerization process of claim 1,wherein the reducing agent is added continuously or periodically to thepolymerization process.
 16. The polymerization process of claim 1,wherein the reduction of the transition metal catalyst complex in adeactivator state is to the transition metal catalyst complex in theactivator state by the reducing agent does not result in formation of anacid.
 17. The polymerization process of claim 1, wherein the reducingagent and catalyst complex act to remove oxygen from the reaction mediumor reaction environment.
 18. The polymerization process of claim 17,wherein the ligand is present from greater than a stoichiometric amountrelative to the transition metal to 10 times a stoichiometric amountrelative to the transition metal.
 19. The polymerization process ofclaim 17, wherein the ligand is present from greater than astoichiometric amount relative to the transition metal to 3 times astoichiometric amount relative to the transition metal.